m04$589h$ wustl/wusm$pioneers$in$neuroscience$...

M04 589H WUSTL/WUSM Pioneers in Neuroscience

Spring 2014 Page 1 of 55

WUSM/WUSTL Pioneers in Neuroscience Objective: Understand origins of this relatively new discipline and gain

perspectives for its increasing impact on medicine in the future. Location: Bernard Becker Medical Library Archives and Rare Books (ARB) -‐ 7th

Floor; Center for History Of Medicine – 6th Floor Bernard Becker Medical Library

Time: 3:30 – 5:30 pm Format: 3:30 – 4:00 pm

4:00 – 5:15 pm: Students present and discuss assigned readings. 5:15 – 5:30 pm: All students write and turn in a short paragraph

(gobbet) on the topic. Readings: Article PDFs for each session are posted on MedPortal. All students

should glance at all materials prior to each session. Participants: Mr. Moises Arriaga, Ms. Diane Aum, Mr. Giuseppe D’Amelio, Mr. Chad

Donahue, Ms. Rachel Gartland, Mr. James Ko, Mr. Ramin Lalezari, Ms. Angela Lin, Mr. Brandon Rogalski, Ms. Rose Tang, Mr. Ethan Tobias, Mr. Nai Yeat

Becker Library Archives and Rare Books Staff: Ms. Elisabeth Brander – Rare Book

Librarian; Mr. Stephen Logston – Archivist; Ms. Martha Riley – Rare Books Cataloger & Archivist; Mr. Phillip Skroska – Visual and Graphic Archivist

Faculty: Robert M. Feibel, MD – Professor of Clinical Ophthalmology & Visual

Sciences; William Landau, MD – Professor Emeritus of Neurology; Joseph L. Price, DPhil - Lecturer Anatomy and Neurobiology, Eugene H. Rubin, MD/PhD – Professor of Psychiatry; Thomas A. Woolsey, MD – Professor of Experimental Neurological Surgery and Acting Director of the Center for History Of Medicine; various other faculty as available.

_______________ Contact Ms. Debra Knox Deiermann 362-‐2725, [email protected] for clarifications, schedule issues, etc.



Schedule: Session Goals General What is now termed “Neuroscience” has its origins in many different academic backgrounds from distinctive disciplines of medicine, engineering and science. These include: Anatomy, Histology, Physiology, Pathology, Medicine, Surgery, Psychiatry, and Radiology as well as undergraduate disciplines of Biology, Chemistry, Engineering, Psychology, and Physics. Washington University was a leader in integrating these different disciplines, in part because of excellence and leadership of individual faculty (several Nobel Laureates) and in part because of exceptional interactions across different disciplines. This selective may engage witnesses to the growth and integration of different aspects of Neuroscience from several departments including – Anatomy and Neurobiology, Neurology, Neurological Surgery, Psychiatry and Radiology – in discussions of major advances in understanding the nervous system and its disorders. All are free to “swap” summaries with fellow students to better match your interests, schedules, etc. We ask that you let Ms. Debra Knox Deiermann know so we can keep track of who’s presenting what.



References: -‐-‐-‐-‐-‐-‐-‐-‐-‐. 1995. In memoriam and memorial service – Eli Robins, M.D.: February 22, 1921-‐Decemeber

21, 1994. Ann Clin Psychiat 7:1-‐10. -‐-‐-‐-‐-‐-‐-‐-‐-‐. 2013. Charles E. Molnar – 14 March 1935-‐13 December 1996.

[http://www.cse.wustl.edu/history/molnar_c/molnar.html] -‐-‐-‐-‐-‐-‐-‐-‐-‐. 2013. Charles Molnar. [http://en.wikipedia.org/wiki/Charles_Molnar] -‐-‐-‐-‐-‐-‐-‐-‐-‐. 2013. H. Richard Tyler, MD -‐ Brigham and Women's Hospital.

[https://www.doximity.com/pub/h-‐tyler-‐md] -‐-‐-‐-‐-‐-‐-‐-‐-‐. 2013. The H. Richard Tyler Collection of the American Academy of Neurology. Library.

[http://beckerexhibits.wustl.edu/rare/collections/tyler.html] Bishop GH. 1944. The structural identity of the pain spot in human skin. J Neurophysiol., 7:185-‐98. Bishop GH. 1944. The peripheral unit for pain. J Neurophysiol 7:71-‐80. Bishop GH. 1965. My Life among the Axons. Ann Rev Physiol 27:1-‐18. Bishop GH, Erlanger J, Gasser HS. 1926. Distortion of action potentials as recorded from the nerve surface.

Am J Physiol 78:592-609. Bishop GH, Erlanger J. 1926. The effects of polarization upon the activity of vertebrate nerve. Am J

Physiol, 78:630-57. Bodian D. 1973. George William Bartelmez 1885-‐1967. Biogr Mem Natl Acad Sci pp. 1-‐26

[http://www.nasonline.org/publications/biographical-‐memoirs/memoir-‐pdfs/bartelmez-‐george.pdf]

Bucholz KK, Cottler LK. 2010. In memoriam – Lee Nelken Robins, PhD. Alcohol Clin Exp Res 34:197-‐198.

Chase MW, and Hunt CC. 1995. Herbert Spencer Gasser -‐ July 5, 1888-‐May 11, 1963. Biogr Mem Natl Acad Sci 67:147-‐177.

Clark WA, Molnar CE. 1964. The LINC: a description of the laboratory instrument computer. Ann N Y Acad Sci, 115:653-‐668.

Cloninger CR. 2001. In memoriam: Samuel B. Guze, MD – 18 October 1923-‐19 July, 2000. Am J Med Genet B Neuropsychiatr Genet 105:1-‐3.

Cohen SB. 1986. Stanley Cohen - Biographical. [(/nobel_organizations/nobelfoundation/publications/lesprix.html)/(NobelLectures/nobel_organizations/nobelfoundation/publications/lectures/index.html)]

Cohen S. 1960. Purification of a nerve-‐growth promoting protein from the mouse salivary gland and its neuro-‐cytotoxic antiserum. Proc Natl Acad Sci USA 46:301–311.

Cohen S, Levi-‐Montalcini R, Hamburger V. 1954. A nerve growth stimulating factor isolated from sarcomas 37 and 180. Proc Natl Acad Sci USA 40:1014–1018.

Cowan WM. 1979. The development of the brain. Scientific American 241:113-‐133. Cowan WM. 2001. Viktor Hamburger and Rita Levi-‐Montalcini: the path to the discovery of nerve

growth factor. Ann Rev Neurosci 24:551-‐600. Cowan WM , (Stanfield B). 2004. William Maxwell (Max) Cowan. The History of Neuroscience in

Autobiogaphy. Volume 4. 146-‐208. Cowan WM, Gottlieb DI, Hendrickson AE, Price JL, Woolsey TA. 1972. The autoradiographic

demonstration of axonal connections in the central nervous system. Brain Res 37:21-‐51. Cowan WM, Guillery RW, Powell TPS. 1964. The origin of the mammilary peduncle and other

hypothalamic connexions from the midbrain. J Anat (Lond) 98:345-363. Cowan WM, Powell TPS. 1954. An experimental study of the relation between the medial mammillary

nucleus and the cingulate cortex. Proc R Soc Lond Ser B 143:114-‐125. Cowan WM, Powell TPS. 1963. Centrifugal fibres in the avian visual system. Proc R Soc Lond Ser B

158:232-‐252. Davis H. 1970. Joseph Erlanger, January 5, 1874-‐December 5, 1965. Biogr Mem Natl Acad Sci 41:111-‐

139.



Galambos R, Davis H. 1943. The response of single auditory-‐nerve fibers to acoustic stimulation. J

Neurophysiol 6:39-‐57. Galambos R. 1998. Hallowell Davis, 1896-‐1992. Biogr Mem Natl Acad Sci pp. 1-‐23.

[http://www.nasonline.org/publications/biographical-‐memoirs/memoir-‐pdfs/davis-‐hallowell.pdf]

Grubb RL. 1999. Henry G. Schwartz, M.D. 1909-‐1998: An obituary. J Neurosurg 90:599-‐602. Grubb RL. 2005. Sidney Goldring, M.D., 1923-‐2004: An obituary. J Neurosurg 102:577-‐579. Grubb RL. 2011. A commitment to excellence: Sidney Goldring and Neuroscience 1974-‐89. Chapter 9.

In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 199-‐244.

Grubb RL. 2011. Henry Schwartz and the neurosurgery residency, 1946-‐74. Chapter 6. In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 141-‐190.

Grubb RL. 2011. Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. 442 pp.

Grubb RL. 2011. The founder of neurosurgery at Washington University: Ernest Sachs, 1911-‐46. Chapter 3. In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 41-‐110.

Guze SB. 1989. Biological psychiatry: is there any other kind? Psychol Med 19:315-‐323. Hamburger V. 1934. The effects of wing bud extirpation on the development of the central nervous

system in chick embryos. J Exp Zool 68:449–494. Hamburger, V. 1958. Regression versus peripheral control of differentiation in motor hypoplasia. Am

J Anat, 102:365-‐409. Hamburger, V. 1975. Cell death in the development of the lateral motor column of the chick embryo. J

Comp Neurol, 160:535-‐546. Hamburger, V. (1977). The developmental history of the motor neuron. Neurosci Res Program Bull, 15

Suppl, iii-‐37. Horrax, G. 1949. Ernest Sachs. J Neurosurg 6:3-‐5. Hudgens RW, Murphy GF. 1995. Eli Robins, MD: February 22, 1921, to December 21, 1994. Arch Gen

Psychiatry 52:1080-‐1081. Hunt CC, Kuffler SW. 1951. Further study of efferent small nerve fibers to mammalian muscle

spindles: multiple spindle innervation and activation during contraction. J Physiol 113:283-‐297.

Hunt CC, Kuffler SW. 1951. Stretch receptor discharges during muscle contraction. J Physiol 113:298-‐315.

Hunt CC, Wilkinson RS, Fukami Y. 1978. Ionic basis of the receptor potential in primary endings of mammalian muscle spindles. J Gen Physiol302:683-‐698.

Hunt CC. 1955. Monosynaptic reflex response of spinal motoneurons to graded afferent stimulation. J Gen Physiol 38:813-‐852.

Hunt CC. 1990. Mammalian muscle spindles: Peripheral mechanisms. Physiol Rev 70: 643-‐663. Hunt CC. 2006. Carlton C. Hunt. The History of Neuroscience in Autobiogaphy. Volume 5. pp. 352-‐380. Iversen LL. 2013. Rita Levi-‐Montalcini: Neuroscientist par excellence. Proc Natl Acad Sci U S A

110(13): 4862-‐4863. Kim DK, Molnar CE, Pfeiffer RR. 1973. A system of nonlinear differential equations modeling basilar-‐

membrane motion. J Acoust Soc Am., 54:1517-‐1529. Kuffler SW, Hunt CC, Quilliam JP. 1951. Function of medullated small nerve fibers in mammalian

ventral roots: Effect muscle spindle innervation. J Neurophysiol 14:29-‐54. Kunkler V. 1996. Michel M. Ter-‐Pogossian (1925-‐1996). Focal Spot. Vol 27.

[http://beckerexhibits.wustl.edu/mig/bios/terpogossian.html] Landau WM. 1976. Obituary: James L. O’Leary, Ph.D., M.D., (1904-‐1975). J Neurol. Sci 28:255-‐57. Landau WM. 1985. George Holman Bishop: June 27, 1889 -‐ October 11, 1973. Biogr Mem Natl Acad

Sci 55:45-‐66. Levi-‐Montalcini R, Booker B. 1960. Excessive growth of the sympathetic ganglia evoked by protein



isolated from mouse salivary glands. Proc Natl Acad Sci USA 46 :373–384.

Levi-‐Montalcini R, Cohen S. 1956. In vitro and in vivo effects of a nerve growth-‐stimulating agent isolated from snake venom. Proc Natl Acad Sci USA 42:571–574.

Levi-‐Montalcini, R., & Hamburger, V. 1951. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 116:321-‐361.

Levi-‐Montalcini R, Meyer H, Hamburger, V. 1954. In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res 14:49-‐57.

Lorente de Nó R. 1943. Cerebral cortex: architecture, intracortical connections, motor projections. Chapter XV. In: JF Fulton, Physiology of the Nervous System. Oxford: New York, pp. 274-‐313.

Marshall LM, Magoun HW. 1990. The Horsley-‐Clarke stereotaxic instrument: The beginning. Kopf Carrier October 1990, pp. 1-‐5.

Morris JC, Landau WM. 2007. In memoriam: Leonard Berg, MD (1927-‐2007). Neurol 69:1206-‐1207. O'Leary J, Heinbecker P, Bishop GH. 1934 Analysis of function of a nerve to muscle. Am J Physiol

110:636-‐658. Purves D. 2001. Viktor Hamburger 1900-‐2001. Nat Neurosci 4:777-‐778. Robins E, Guze SB. 1970. Establishment of diagnostic validity in psychiatric illness: its application to

schizophrenia. Am J Psychiat 126:983-‐987. Sabin FR. 1944. Stephen Walter Ranson 1880-‐1942. Biogr Mem Natl Acad Sci 23:364-‐397. Schwartz HG, and O’Leary JL. 1941. Section of the spinothalamic tract in the medulla with

observations on the pathway for pain. Surgery 9:183-‐193. Ter-‐Pogossian M, Raichle ME, Sobel BE. 1980. Positron-‐emission tomography. Scientific American

243:170-‐181. Van Essen DC, Price JL. 2002. Obituary: W. Maxwell Cowan (1931-‐2002). Nature 418:600. Wann DF, Price JL, Cowan WM, Agulnek MA. 1974. An automated system for counting silver grains in

autoradiographs. Brain Res 81:31-‐58. Wann DF, Woolsey TA, Dierker ML, Cowan WM. 1973. An on-‐line digital computer system for the

semi-‐automatic analysis of Golgi-‐impregnated neurons. IEEE Trans Biomed Eng BME-‐20:233-‐247.

Woolsey TA. 2000. Rafael Lorente de Nó, 1902-‐1990. Biogr Mem Natl Acad Sci. 79:85-‐105. Zeliadt N. 2013. Rita Levi-‐Montalcini: NGF, the prototypical growth factor. Proc Natl Acad Sci USA

110:4873-‐4876.



Session I. Wednesday April 9, 2014 -‐ Physiology (Ophthalmology,

Neurology)

Focus: Electrophysiology of sensory neurons. Summarizers: Mr. Yeat ---------. 2013. H. Richard Tyler, MD - Brigham and Women's Hospital.

[https://www.doximity.com/pub/h-tyler-md] ---------. 2013. The H. Richard Tyler Collection of the American

Academy of Neurology Library. [http://beckerexhibits.wustl.edu/rare/collections/tyler.html]

Mr. Tobias Davis H. 1970. Joseph Erlanger, January 5, 1874-December 5, 1965. Biogr Mem Natl Acad Sci 41:111-139.

Ms. Tang Chase MW, and Hunt CC. 1995. Herbert Spencer Gasser - July 5, 1888-May 11, 1963. Biogr Mem Natl Acad Sci 67:147-177.

Mr. Rogalski Landau WM. 1985. George Holman Bishop: June 27, 1889-October 11, 1973. Biogr Mem Natl Acad Sci 55:45-66.

Ms. Angela Lin Erlanger J, Bishop GH, Gasser HS. 1926. Experimental analysis of the simple action potential wave in nerve by the cathode ray oscillograph. Am. J Physiol 78:537-73.

Mr. Lalezari Bishop GH. 1944a. The peripheral unit for pain. J Neurophysiol 7:71-80. Bishop GH 1944b. The structural identity of the pain spot in human skin. J

Neurophysiol 7:185-98. Mr. Ko Bishop GH. 1965. My Life among the Axons. Annu Rev Physiol 27:1-18.



Other references for voluntary consideration: Bishop GH, Erlanger J, Gasser HS. 1926. Distortion of action potentials as recorded from the

nerve surface. Am J Physiol 78:592-609. Bishop GH, Erlanger J. 1926. The effects of polarization upon the activity of vertebrate nerve.

Am J Physiol 78:630-57. Erlanger J, Bishop GH, Gasser HS. 1926. The action potential waves transmitted between the

sciatic nerve and its spinal roots. Am. J Physiol 78:574-91. O'Leary J, Heinbecker P, Bishop GH. 1934. Analysis of function of a nerve to muscle. Am J

Physiol 110:636-658.



ARB Displays

Session I April 9, 2014

Documents: The H. Richard Tyler Collection of the American Academy of Neurology Library H. Richard Tyler (b. 1927) received his medical degree from the Washington University School of Medicine in 1951. He led the Neurology Division at Peter Bent Brigham Hospital in Boston from 1956-‐1988 and is an internationally renowned neurologist at Harvard Medical School. Although neurology became a specialty late in the 19th century, its origins are in early anatomical atlases and general medical works that depict and describe the nervous system, or specifically the brain or the spinal cord. Of the 7,000 volumes in the H. Richard Tyler Collection, the majority are landmarks in neurology and neuroscience. Dr. Tyler’s donation ensures that future neurologists and medical historians will be able to uncover and interpret the beginnings and development of this significant field in medicine. Albertus of Orlamünde, Dominican (fl. late 13th C). Philosophia pauperum. Venetiis: Georgium de Arriuabenis, 1496. The Philosophia pauperum, now generally ascribed to Albertus of Orlamünde, includes extracts from writings of Albertus Magnus (1193?-‐1280). Works by Albertus Magnus were often digested by his students and confrères for the instruction of the less learned brethren. In earlier manuscripts this “Philosophy for the simple” (Philosophia pauperum), as the work was sometimes called, is ascribed only to a “Brother Albert, O.P.” Other manuscripts are more specific, mentioning an “Albert of Orlamünde.” Scholars now believe that it was this Albert (fl. late 13th c.), a Dominican teacher in Thüringen, who compiled these digests, a short textbook of natural philosophy and psychology which was used in schools throughout the Middle Ages. In the chapter about the soul (De anima) the author discusses the three ventricles of the brain as it is represented in the illustration. Vesalius, Andreas (1514-‐1564). Andreae Vesalii Bruxellensis, scholae medicorum Patauinae professoris De humani corporis fabrica libri septem ... -‐ Basileae: Ex officina Joannis Oporini, anno salutis reparatae 1543. Mense Iunio. Vesalius alone made anatomy a living working science. His Fabrica came out of five years experience as public prosector at Padua, where he taught students to discuss and inspect parts in situ. Vesalius was the teacher of Gabriele Fallopio and he became court physician to Charles V in Madrid. Malpighi, Marcello (1628-1694), Fracassati, Carlo (ca. 1630-1672). Epistolae anatomicae virorum clarissimorum Marcelli Malpighii et Caroli Fracassati. Amstelodami: apud C. Commelinum, 1669. A collection of letters compiled by Carlo Fracassati, Malpighi’s friend and colleague at the University of Bologna. Four of the letters written by Malpighi and two by Fracassati are treatises about the brain. Detailed copperplate illustrations represent Malpighi’s microscopic investigations. This image depicts the crosscut of the optical nerve in the Xiphia fish. Willis, Thomas (1621-‐1675). The anatomy of the brain, 1681 edition with the original illustrations by Sir Christopher Wren. Tuckhoe, New York, 1971



Willis, Thomas (1621-‐1675). Opera Omnia. Coloniae: Sumptibus Gasparis Storti, 1694. Willis practiced in Oxford then in London, where he was known as an outstanding physician. In addition to his practice he carried on extensive research and published a number of important works on medicine, anatomy, and pharmacology. His Cerebri anatome or Anatomy of the brain was considered the most complete and accurate account of the nervous system which had hitherto appeared. Christopher Wren, the illustrator and architect, was his student at Oxford. Descartes, René (1596-1650). Tractatus de homine. Amsterdam: Elsevier, 1677. René Descartes, French philosopher, mathematician and scientist, first published his De homine in 1622. He explained the mechanism of the eye in his Dioptrica (1637). He was probably the first to suggest that reflex reactions occurred without any conscious awareness. Bell, Charles (1774-‐1842). The anatomy of the brain explained in a series of engravings. London: Longman and Rees, 1802. Charles Bell was trained in art as well as in medicine, and his twelve plates illustrating the structure of the brain are among the most beautiful in neuroanatomy. Gall, F. J. (1758-‐1828) and Spurzheim, Johann Gaspar (1776-‐1832). Anatomie et physiologie du systéme nerveux en général, et du cerveau en particulier, avec des observations sur la possibilitéde reconnoitre plusieurs dispositions intellectuelles et morales de l'homme et des animaux, par la configuration de leurs têtes, par F. J. Gall et G. Spurzheim ... -‐ Paris, chez F. Schoell, 1810-‐19. -‐-‐Atlas folio edition. -‐-‐ v. 4 quarto edition. This work introduced the theory of localization of cerebral function, although in a somewhat fantastic form. This pioneer attempt to map out the cerebral cortex according to function gave rise to the pseudo-‐science of phrenology. This library has both the quarto and folio text of this first edition. Garrison-‐Morton 1389 Swan, Joseph (1791-‐1874). A demonstration of the nerves of the human body. London: Longman, Rees, Orme, Brown and Green, 1830. Swan’s atlas of neuroanatomy is one of the most beautiful works ever published on the subjects with drawings by E. West that were engraved by William and Edward Finden.. This is the first folio edition. Duchenne, G. Benjamin Amand (1806-‐1875) De l’électrisation localisée. Paris: Bailliére, 1872. Duchenne was one of the earliest researchers working on the electrophysiology of muscles and first published his findings in this monograph, in 1855.



Charcot, Jean-Martin (1825-1893), Oeuvres complètes de J.-M. Charcot. 9 volumes. Paris: Delahaye & Lecrosnier, 1885-. volume. 3 & 9 The greatest of French neurologists, Charcot and his Salpêtrière school brought a new legitimacy to the scientific study of neuroses. t. 3. Leçons sur les maladies du système nerveux, recueillies et publiées par Babinski, Bernard, Féré, Guinon, Marie et Gilles de la Tourette 1890 t.9. Hemorragie et ramollissement du cerveau. Metallo-thérapie et hypnotisme-électrothérapie. 1890. Ramón y Cajal, Santiago (1852-1934). L'anatomie fine de la moelle épinière, mit 8 lithographische Tafeln, 1895 in Atlas der pathologischen Histologie des Nervensystems : herausgegeben von V. Babes [et al.] Redigirt von Dr. V. Babes und P. Blocq. - Berlin : August Hirschwald, 1892-1906 Ramón y Cajal, Santiago (1852-1934). Histologie du système nerveux de l'homme & des vertébrés. Ed. française rev. & mise à jour par l'auteur. Traduite de l'espagnol par L. Azoulay. - Paris: A. Maloine, 1909-1911. Ramón y Cajal, Santiago (1852-1934). Textura del sistema nervioso del hombre y de los vertebrados. Madrid: Imprenta y Librería de Nicolás Moya ..., 1899. – Letter from S. Ramón y Cajal to E.V. Cowdry, Madrid, 23 Febrier 1923. Box 17 Folder 16, E. V. Cowdry Papers, Bernard Becker Medical Library Archives, Washington University School of Medicine. Golgi, Camillo, (1843-1926). Opera omina. Milano: Ulrico Hoepli, 1903. The structure and function of the nerve cells and fibers were clarified through the significant investigations of Camillo Golgi (1843-1926) and Santiago Ramón y Cajal (1852-1934) in the first decade of the twentieth century. Cajal was the teacher of Lorente de Nó who was director of Research for the Central Institute of the deaf in St. Louis. Dandy, Walter Edward (1886-1946) The brain. Chapter 1 In: Lewis Dean’s Practice of Surgery. Hagerstown, MD: W.F. Prior, 1932. Walter Edward Dandy (1886-1946), native of Sedalia, MO, was one of Harvey Cushings’s brilliant pupils and later his personal antagonist, advanced neurosurgery through innovations in surgical technique and diagnostic procedures. Freeman, Walter (1895-1972). Psychosurgery : intelligence, emotion and social behavior following prefrontal lobotomy for mental disorders, by Walter Freeman and James W. Watts. With special psychometric and personality profile studies by Thelma Hunt. - Springfield, IL: Charles C Thomas, 1942. Walter Jackson Freeman II, M.D. was an American physician who specialized in lobotomy. He studied neurology and the University of Pennsylvania Medical School. He earned a PhD in neuropathology. He was a member of the American Psychiatric Association. His partner in psychosurgery was neurosurgeon James Watts (1904-) who performed the actual surgeries.



Images: Joseph Erlanger with nerve potential graph, circa 1922 Joseph Erlanger was born in San Francisco, studied at the University of California and received his medical education at Johns Hopkins University in 1899. He was an intern at the Johns Hopkins University Hospital under William Osler. From 1900 to 1906, he was an Assistant in Physiology at Johns Hopkins under William H. Howell. He became Professor of Physiology at the University of Wisconsin Medical School in 1906. In 1910, he became Professor and Head of the Department of Physiology at Washington University in St. Louis until he retired in 1946. In 1944, he and Herbert S. Gasser were awarded the Nobel Prize in Physiology or Medicine “for … discoveries relating to the highly differentiated functions of nerve fibres.” VC027052 Herbert Gasser Herbert Spencer Gasser was born in Platteville, Wisconsin and attended the University of Wisconsin, receiving his bachelors and masters degrees. It was at this time he first became acquainted with Erlanger. After receiving a doctorate from Johns Hopkins University, he became Professor of Pharmacology in 1921 at Washington University. A decade later, Gasser was appointed Professor of Physiology and Head of the Medical Department at Cornell University in New York City. From 1935 to 1953, he was Director of the Rockefeller Institute for Medical Research. He was awarded the Nobel Prize for Medicine in 1944, along with Joseph Erlanger, for their work with action potentials in nerve fibers. VC027037 Erlanger seated at oscillograph, circa 1940 VC027014 Erlanger and Gasser’s home-‐made cathode ray tube When Erlanger and Gasser began working on the properties of nerve fibers they originally used a string galvanometer which proved to be too slow to register the nerve potentials. They realized that a relatively new instrument, the cathode ray tube oscilloscope invented by Karl Ferdinand Braun, could work. Unable to purchase one from Western Electric they began to build their own cathode ray tube. When they first switched it on there was an explosion – they had forgotten to put in a central controlling resistor. By then, their correspondence with Western Electric paid off and they were able to have a special CRT made for them. VC128009 George H. Bishop, circa 1930 George H. Bishop received his PhD from the University of Wisconsin and joined the faculty of Washington University School of Medicine in 1921. He held a variety of appointments, among them Research Associate and Associate Professor in the Department of Physiology (1921-‐1930), Professor of Applied Physiology in the Department of Ophthalmology (1930-‐1932), Professor of Biophysics in the Neurophysiology Laboratory (1932-‐1947) and Professor of Neurophysiology in the Department of Neuropsychiatry (1947-‐1954). Dr. Bishop is remembered for his collaboration with Joseph Erlanger and Herbert S. Gasser in research on the properties of nerve fibers, for which the latter two received the 1944 Nobel Prize in Physiology or Medicine. Dr. Bishop is also well-‐known for his work in the development of electroencephalography as a diagnostic tool in the understanding of epilepsy. VC034043



Erlanger J, Gasser H, (Bishop G) The compound nature of the action current of nerve as disclosed by the cathode ray oscillograph, Reprint. American Journal of Physiology v. 70, no. 3 (November 1924) Joseph Erlanger Papers (FC001), Series 7, Publications, Box 33, [Bound volume] Reprints, Erlanger (II) 1912-‐1924 Helen T. Graham in her lab, circa 1950 Helen Treadway Graham received her PhD from the University of Chicago. She joined the Department of Pharmacology where she worked closely with Gasser, Erlanger and Bishop on the early research on nerve conduction. VC049087 Peter Heinbecker Peter Heinbecker was a surgical trainee under Evarts Graham, the Head of the Department of Surgery. Graham, the husband of Helen Treadway Graham, recommended that Heinbecker do the research component of his training with George Bishop. Heinbecker and Bishop would make important discoveries concerning the C wave of unmyelinated nerve fibers. However, his work with Bishop would also create difficulties with Erlanger over who had investigative primacy over the nerve research. VC410HeinbeckerP James L. O’Leary James L. O’Leary received his PhD in Anatomy from the University of Chicago in 1928. He continued his studies to earn an MD also from the University of Chicago in 1931. After receiving his MD, O’Leary came to Washington University School of Medicine. By the early 1940s he held joint appointment as Associate Professor of Anatomy and of Neurology, eventually becoming the Head of the Department of Neurology. During his time with the department, he extensively studied nerve physiology, pain mechanisms, and the clinical and electroencephalographic aspects of epilepsy. VC410OLearyJL Various publications from the continued research on nerve fibers by Bishop, Heinbecker, and O’Leary James L. O'Leary Papers FC021, Series 18: Publications Box 47 Folder 5: Reprints, 1932. George Bishop at home with his wife and colleague, Ethel Ronzoni. Ronzoni received her PhD in Physiology from the University of Wisconsin in 1923. She came to Washington University in 1923 as Assistant Professor in Biochemistry. She also ran the chemistry lab of the Department of Medicine and Barnes Hospital. VC034014 George Bishop with the Head of Neurosurgery, Henry G. Schwartz. VC034036 Cartoon and poem authored by George Bishop VC034034



M04 589H – Pioneers in Neuroscience Gobbets

Session I April 9, 2014

Faculty: Drs. Feibel, Landau & Woolsey

What I found most interesting was the collaboration and general politics that took place in working toward these major discoveries. The disparate backgrounds of the different scientists seemed to be integral in providing the perspectives necessary to accomplish the work. Also, the experiments Bishop performed on himself are very different from the way that experiments are done/allowed to happen today. I continue to be amazed by the insight and intellectual capacity it must have taken to research in an otherwise mystical and unknown field. The readings for this week showed how successful Drs. Erlanger, Gasser, Bishop, and Tyler all were and how their groundbreaking research, which seems so basic to us now, with limited resources and a lack of background knowledge. It seems crazy that researchers like Bishop did so many experiments on themselves. It was also really cool to have Dr. Landau here to speak with us and give us a personal take on the people and subjects we’re learning about. The history and progression of science is fascinating. Seeing real signatures and aging photographs bring to life the topics learned in sometimes mundane lecture halls. After today, I felt as though I had spent two hours with Erlanger, Gasser, and Bishop themselves. I really enjoyed hearing biographies of these revolutionary scientists before reading their papers; I believe context puts their discoveries in perspectives I have never experienced.



With our first session we discussed some of the first investigators looking into the electrical properties of the neuron. I'm fascinated by the ways in which they were able to capture the rapid, non-‐linear, and non-‐periodic activity of neurons with extremely early technology. The amount of careful engineering required to get a good quality signal with a home made cathode ray tube is extremely impressive, especially when they were relying on passive components such as a wheat-‐stone bridge for signal stabilization. Today, we learned about Drs. Tyler, Erlanger, Gasser and Bishop who laid the groundwork for what would later become the field of neurology. They played especially pivotal roles in establishing neuroscience and neurology as a field in the United States, since in the years that they were active, neurology was not yet an established field in the United States though it was more established in the United Kingdom and Europe. It was very interesting to hear the personal anecdotes supplied by Dr. Landau on the characters of Dr. Erlanger et al. Dr. Landau’s stories added a lot of color to today’s session, and I look forward to the coming sessions. The readings for this week’s Pioneers in Neuroscience were interesting because many of the people who were making developments in the field did not begin their careers in biology or medicine. We read about a few individuals who were officially trained in electrical engineering, and one person who was actually trained in literature. When thinking about the field of neurology now, it seems strange that its heyday was organized and run by people without medical training. It can catch one off guard to learn that a field that is so specialized originally began with people who had no idea what they were doing, and were even experimenting on themselves. To hear that Bishop was cutting parts of his skin out in order to learn more about sensation seems quite the opposite from the high tech imaging research that is conducted today. The readings from this week remind me that it is important to look back and realize that what we think of as the epitome of knowledge and understanding, trying to understand what the brain is made of, originally began as raw, barely understood experiments.



We discussed today about some of the first steps in research towards the discovery of functions of the nervous system, in particular peripheral neurons, and those whose work was instrumental in this matter. What was most striking was that many of these scientists, while they made great discoveries and seem almost mystical in the way they are discussed now, had many human aspects, varying personalities but also some flaws. We also discussed research that was contemporary at the time and about what they viewed as the future of neuroscience, in particular discussions about the physiology of itch and the evolution and function of various nerve fibers between vertebrates and invertebrates. Here at WashU, people know the names of Nobel laureates Erlanger and Gasser, but we usually only hear about their scientific work. Today we had the chance to hear about another side – personalities and politics – from Dr. Landau. Dr. Landau’s mentor, George Bishop, made essential contributions to the studies of the compound action potential, for which his co-‐authors Erlanger and Gasser received the Nobel Prize, and Dr. Landau’s anecdotes regarding these three men were most illuminating concerning this situation. As students, most of us have done research using various digital technologies, and it was interesting (and impressive) to take a closer look at research accomplished using what now seem to be quite rudimentary techniques, as well as to peek into the lives of these three researchers. I am especially impressed with the ingenuity and foresight all of the various pioneers we discussed today. With very limited equipment and neurophysiological knowledge, Erlanger, Gasser and Bishop developed complex theories regarding the neuron itself and the action potentials they produce with startling detail. Learning about Dr. Bishop particularly moved me. I found it fascinating that he developed the theory on pain fibers by experimenting on himself. It’s incredible that someone would perform skin biopsies and inject himself with turpentine to create an immunological reaction all for the sake of studying pain receptors. It seems to me that scientific research during that period was raw and tangible and that kind of research excites me a lot more than the computer-‐driven data analytics that dominates today. Call me old school but I’m partial to Bishop’s “Wild West” techniques.



From the first session we learned about several WUSM faculty, their lives, and their contributions to our current understanding of neuroscience. We discussed the work of Drs. Erlanger, Gasser, Tyler, and Bishop. My assigned reading was a memoir of Dr. Gasser, and through the memoir I was able to gain an understanding and appreciation of both the work Dr. Gasser accomplished and the kind of person he was. I also had the opportunity to hear from my classmates their summaries of the work of Dr. Bishop and Erlanger. Finally, I was able to look at the various books and original publications of these researchers and even the original cathode ray Drs. Erlanger and Gasser built, which allowed me to better put the work they have done in perspective. It was very interesting hearing about the interactions between research staff members at Wash U when the field of neurophysiology was just beginning. In the new and obscure field of neurophysiology, the research methods and approaches seemed particularly creative. I was simultaneously impressed and amused by how Dr. Bishop studied the structure of synapses by performing experiments and biopsies on his own skin. Drs. Erlanger, Gasser and Bishop were among the preeminent pioneers in the neurosciences and contributed greatly to the field. They came together at Washington University School of Medicine in the early 1920s and using the newly invented cathode ray tube were able, with great difficulty, to make recordings of nerves. Their research revealed several different types of nerve fibers with differing velocities. What I learned from this discussion was that there was a major power struggle among the researchers, especially since Dr. Erlanger, as head of the department of Physiology, controlled the publications of his other researchers. Later, only Drs. Erlanger and Gasser were awarded the Noble prize, although they shared the prize money with Dr. Bishop recognizing his contribution. The researchers parted ways, and Dr. Bishop later worked at Rockefeller on the units of pain sensation. In order to conduct his research, Dr. Bishop used himself as a subject and amazingly removed patches of his own skin in the name of science. I am fascinated by their contributions to the medical science and the interesting facets of their personal lives.



Session II. Wednesday April 16 – Zoology & Biochemistry, aka

Neuroembryology

Focus: Discovery of nerve growth factor (NGF). Summarizers: Mr. Yeat Purves D. 2001. Viktor Hamburger 1900-2001. Nat Neurosci 4:777-778.

Iversen LL. 2013. Rita Levi-Montalcini: Neuroscientist par excellence. Proc Natl Acad Sci U S A 110: 4862-4863.

Zeliadt N. 2013. Rita Levi-Montalcini: NGF, the prototypical growth factor. Proc Natl Acad Sci U S A 110:4873-4876.

Cohen SB. 1986. Stanley Cohen - Biographical. [(/nobel_organizations/nobelfoundation/publications/lesprix.html)/(NobelLectures/nobel_organizations/nobelfoundation/publications/lectures/index.html)]

Mr. Tobias Hamburger V. 1934. The effects of wing bud extirpation on the development of the central nervous system in chick embryos. J Exp Zool 68:449–494.

Ms. Gartland Hamburger, V. 1975. Cell death in the development of the lateral motor column of the chick embryo. J Comp Neurol, 160, 535-546.

Mr. Donahue Mr. D’Amelio Cohen S, Levi-Montalcini R, Hamburger V. 1954. A nerve growth

stimulating factor isolated from sarcomas 37 and 180. Proc Natl Acad Sci USA 40:1014–1018.

Mr. Arriaga Cowan WM. 2001. Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor. Ann Rev Neurosci 24:551-600.



Other references for voluntary consideration: Cohen S. 1960. Purification of a nerve-growth promoting protein from the mouse salivary gland

and its neuro-cytotoxic antiserum. Proc Natl Acad Sci USA 46:301–311.Hamburger, V. 1958. Regression versus peripheral control of differentiation in motor hypoplasia. Am J Anat 102:365-409.

Hamburger, V. (1977). The developmental history of the motor neuron. Neurosci Res Program Bull, 15 Suppl, iii-37.

Levi-Montalcini R, Booker B. 1960. Excessive growth of the sympathetic ganglia evoked by protein isolated from mouse salivary glands. Proc Natl Acad Sci USA 46:373–384.

Levi-Montalcini R, Cohen S. 1956. In vitro and in vivo effects of a nerve growth-stimulating agent isolated from snake venom. Proc Natl Acad Sci USA 42:571–574.

Levi-Montalcini R, Hamburger V. 1951. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 116: 321-361

Levi-Montalcini R, Meyer H, Hamburger V. 1954. In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res 14:49-57.



Session II -‐ April 16, 2014

Faculty: Drs. Feibel, Landau & Woolsey

We discussed again, a trio of collaborators in neuroscience research at WashU, two of whom received the Nobel Prize, leaving out one who arguably made similar or greater contributions (apparently not an uncommon occurrence, as a result of academic politics). For their isolation of nerve growth factor (NGF), Rita Levi-‐Montalcini and Stanley Cohen shared the Nobel Prize in 1986, excluding Viktor Hamburger, who had started the project with Levi-‐Montalcini and introduced her to sarcoma 180, a mouse tumor with nerve-‐growth-‐inducing properties that she and Cohen used to study nerve growth in chick ganglia. WashU appears to have benefited indirectly from the influence of Nazi Germany and Mussolini in Italy, since Hamburger stayed in the US after the Nazi party revoked his instructorship at the University of Freiburg due to his Jewish heritage, and Levi-‐Montalcini’s academic career in Italy was cut short by Mussolini’s, similarly anti-‐Semitic, Manifesto of Race. This session’s discussion focused on the lives and works of Drs. Viktor Hamburger, Rita Levi-‐Montalcini, and Stanley Cohen. Dr. Hamburger was widely recognized for his contributions to embryology and developmental neuroscience. His major accomplishments involved work on the normal cell death that occurred as part of the normal nervous system developmental process in chick embryos. In addition, he showed that neurons depended on their peripheral targets to thrive and grow. Drs. Cohen and Levi-‐Montalcini collaborated under the leadership of Dr. Hamburger to isolate the NGF that Dr. Levi-‐Montalcini had discovered under Dr. Hamburger’s supervision. I was very impressed with and inspired by Dr. Levi-‐Montalcini’s dedication to research and discovery, going so far as to build an in-‐home laboratory at a time when she wasn’t allowed to pursue her career. Like many, I found it unfortunate that the Nobel Committee failed to appreciate the significance of Dr. Hamburger’s contributions, which paved the way to the later discoveries of Drs. Levi-‐Montalcini and Cohen. This made me contemplate the criteria and politics that are involved as well as the many controversies that surround the committee and decision process.



So much of modern research involves searching for genetic point mutations or specific isoforms of proteins that I would not even know how to approach experiments like Viktor Hamburger and Rita Levi-‐Montalcini’s. The methods they used seem so innovative and creative, especially since they didn’t have much to base their science or methods on. There must only be a couple people in the world that would think to use snake venom to degrade the nucleic acid part of a protein that can then be applied to neural growth research. My favorite part of this session was actually learning about how World War II caused so many brilliant scientists to relocate and end up at WashU. I’m really glad that someone pays me to do research over the summer and I won’t have to hide in my attic. I thoroughly enjoyed learning about the exciting history of the discovery of nerve growth factor. Discussing a protein in this context opens my eyes to the stories of the molecules that often get glossed over in lectures. I felt a feeling similar to when you gaze upon a crowded city square and humbly recognize that each person walking before you has a story. So too, do each of the molecules that are discussed in our lectures. Each has a riveting story of hard work and triumph in their discoveries. I was struck by the serendipitous fashion in which some of these discoveries took place. It really highlighted the importance not just of strong theoretical backing but of a willingness to examine new sources of information in research. It would have been very easy to Hamburger at multiple times to ignore contrary opinions from Levi-‐Montalcini or not to follow up on a result which did not support his beliefs. Instead, through a strong sense of curiosity and willingness to discover the truth, regardless of the outcome, this important discovery was made.



Today we discussed the many years of research that led to the discovery of nerve growth factor, which was found to be extremely important in the development of the peripheral nervous system. What was most interesting was that many of the experiments seemed to be based on seemingly random components. For example, mouse sarcomas implanted in chick embryos were found to maintain the proliferation of neurons in that area. Also, snake venom was eventually found to have a profound nerve growth effect. From this, NGF was eventually isolated from that venom. We also discussed the nature of its discovery and how credit, with particular focus on the Nobel prize, was given to researchers and how Dr. Hamburger, whose research was instrumental in the discovery of NGF, was not awarded the Nobel Prize. We finally discussed the implications this research had for similar types of research, such as in angiogenesis, which have great relevance to our knowledge of the pathogenesis and treatment of cancer today. One of the most impressive components of this week’s readings is the intuition behind the research that revealed Nerve Growth Factor and nerve development. Nowadays we focus so much on the amount of information made available via the internet, computer models, and extremely complex organizational systems in experiments that we forget the simplicity and intuition that resulted in major developments in years past. The example where Cohen, Hamburger, and Levi-‐Montalcini saw sarcomas resulting in nerve proliferation and hyperplasia and simply kept repeating the experiment with different components of the sarcoma show how a well designed and simple experiment can have profound effects. They just kept purifying the sarcomas down to smaller and smaller components until they arrived at the substance they were looking for. They did not need crystallography, computational modeling, etc. Of course, these are important tools; these early experiments revealed that a factor existed, however, it shed little to no light on how the factors worked molecularly. It is important to look back and see the previous steps in science’s advancements. By better understanding how Nerve Growth Factor was discovered and purified, we might be better able to understand our own molecular research.



The stories of Drs. Hamburger, Levi-‐Montalcini, and Cohen, were fascinating, both because of their significant contributions to the field of neuroscience leading to the discovery of NGF and because of their personal narratives. I was particularly moved by how both Drs. Hamburger and Levi-‐Montalcini faced persecution in their native European countries because of their identity and were fortunate enough to get past those experiences. The story of Dr. Levi-‐Montalcini’s secret laboratory in Mussolini run Italy showed how she risked her life to pursue science. I also found the story of the serendipitous discovery of NGF in rattlesnake venom to be interesting and an important reminder to us, as future physician-‐scientists, not to disregard incidental findings and to pursue them, because they might turn out to be particularly important. Today, we learned about the discovery of nerve growth factor, an important discovery, not just in the field of neuroscience, but also in the field of modern cell biology, as Nerve Growth factor (NGF) was the first diffusible growth factor to be discovered. My biggest takeaway from today’s session was the fact that while scientific breakthroughs often happen as the result of serendipity, the groundwork for such serendipity (which is often invisible) is laid over the course of many years, and sometime, many generations of researchers. For example, Montalcini and Cohen’s discovery of nerve growth factors was helped along by the fact that they stumbled upon snake venom and mouse salivary glands, but most would agree that their findings were built on Viktor Hamburger’s earlier work. Hamburger’s work in turn, was possible only because of the earlier work done by Frank Lillie on chick embryos (Viktor Hamburger used the techniques that he learned at Lillie’s lab for more than 50 years).



Session III. Wednesday April 23 -‐ Neurosurgery, Neurology and

Psychiatry

Focus: Development and transformation of Neurological Surgery, Neurology and

Psychiatry. Summarizers: Ms. Aum Sabin FR. 1944. Stephen Walter Ranson 1880-1942. Biogr Mem Natl

Acad Sci. 23:364-397. Mr. Donahue Bodian D. 1973. George William Bartelmez 1885-1967. Biogr Mem Natl

Acad Sci. 43: 1-26 Ms. Tang Horrax, G. 1949. Ernest Sachs. J Neurosurg 6:3-5.

Marshall LM, Magoun HW. 1990. The Horsley-Clarke stereotaxic instrument: The beginning. Kopf Carrier. October 1990, pp. 1-5.



Mr. Rogalski Landau WM. 1976. Obituary: James L. O’Leary, Ph.D., M.D., (1904-

1975). J Neurol Sci 28:255-57. Grubb RL. 1999. Henry G. Schwartz, M.D. 1909-1998: An obituary. J

Neurosurg 90:599-602. Grubb RL. 2005. Sidney Goldring, M.D., 1923-2004: An obituary. J

Neurosurg 102:577-579. Morris JC, Landau WM. 2007. In memoriam: Leonard Berg, MD (1927-

2007). Neurol 69:1206-1207. Mr. Yeat -----------. 1995. In memoriam and memorial service – Eli Robins, M.D.:

February 22, 1921-Decemeber 21, 1994. Ann Clin Psychiat 7:1-10. Hudgens RW, Murphy GF. 1995. Eli Robins, MD: February 22, 1921, to

December 21, 1994. Arch Gen Psychiatry 52:1080-1081. Mr. Ko Bucholz KK, Cottler LK. 2010. In memoriam – Lee Nelken Robins,

PhD. Alcohol Clin Exp Res 34:197-198. Cloninger CR. 2001. In memoriam: Samuel B. Guze, MD – 18 October

1923 - 19 July, 2000. Am J Med Genet (Neuropsychiat Genet) 105:1-3.

Ms. Gartland Robins E, Guze SB. 1970. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiat 126: 983-987.

Mr. Donahue Guze SB. 1989. Biological psychiatry: is there any other kind? Psychol Med 19:315-323.

Other references for voluntary consideration: Grubb RL. 2011. A commitment to excellence: Sidney Goldring and Neuroscience 1974-89.

Chapter 9. In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 199-244.

Grubb RL. 2011. Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. 442 pp.

Grubb RL. 2011. The founder of neurosurgery at Washington University: Ernest Sachs, 1911-46. Chapter 3. In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 41-110.

Grubb RL. 2011. Henry Schwartz and the neurosurgery residency, 1946-74. Chapter 6. In: Neurosurgery at Washington University: A Century of Excellence. The Washington University on behalf of its Department of Neurosurgery. pp. 141-190.



Session III -‐ April 23, 2014

Faculty: Drs. Feibel, Landau, Rubin & Woolsey

I have noticed that many of the scientists we’ve discussed in this class have started out as zoologists, which is intriguing to me. With the residency match system and strictly structured career path for us today, it can seem like we get locked into specialties – it is good to remember that we can take very different paths later in life. For those who definitely know what they want to go into, however, the accelerated wartime premedical programs that we’ve heard about in various peoples’ training sounds really cool. Not that war is cool, but accelerated programs are a cool idea for medical training during times in which medical professionals are in high-‐demand. I would totally sign up for that. I also liked the shout-‐out to my alma mater, the University of Pittsburgh, when we talked about Dr. Goldring. It’s good to hear Pitt’s name among the super famous greats like WashU, Chicago, and Hopkins. Although talking about all these people who got their M.D. at age 21 makes me feel old… This week we discussed many of Washington University’s early neurologists, neurosurgeons and psychiatrists. One of the early facts that struck me was how many of the physicians we studied trained in Dr. Bishop’s physiology lab. When we discussed Bishop in the first week, it was apparent that he made many important discoveries as a scientist but I would argue that his most important contribution to society might have been the training of future clinician-‐scientists. Continuing with this theme, I thought it was impressive just how committed many of these doctors were to the training and mentoring of future physicians. Switching gears, it was noted that many of these pioneers were recruited into the military during WWII and I think it would be interesting to see how much of an impact this event made on both their individual careers but also on the fields of neurosurgery and neurology themselves. I know that many of the great advancements in medicine have come from war and I would imagine that this paradigm holds true for WWII and the neurosciences.



I found the stories about the individual researchers’ personal idiosyncracies particularly compelling. For the example, I found interesting the story of Dr. O’Leary kicking the exposed film canisters down the corridor or the story of Dr. Sachs and the way he chided a student for not knowing to use a flashlight to diagnose an enlarged scrotum. I also found their personal histories particularly fascinating. For example, it was impressive that Dr. Schwartz volunteered to serve in WW II after visiting Germany and seeing what was going on there. It was also interesting how Dr. Berg became very involved in medical research after leaving private practice. This is definitely not a normal career move but it shows what an incredible clinician and leader in Alzheimer’s research he was. Medicine and medical research now is firmly interdisciplinary, and it’s hard for me to imagine a time when anatomy and physiology were studied strictly separately, so it’s interesting to hear about neuroscientists who worked at the start of this interdisciplinary era, when experimental neurosurgical procedures were intertwined with research. Since we just started learning about the somatosensory system in lecture, reading about Schwartz’s medullary tractotomy as treatment for intractable pain was particularly interesting (even though I didn’t get to share my excitement this week). I really liked hearing about which of these notable neuroscientists were Dr. Landau’s friends and classmates – I wonder which of my former or present classmates will end up as prolific scientists!



Today’s session focused on prominent figures in the development of neurosurgery, neurology, and psychiatry. I had the opportunity to learn about the contributions of various WUSM faculties to these fields of neuroscience. I noticed that many of these faculty considered one of their greatest accomplishments the training of residents and students under them, many of whom went on to serve as leaders in the field. I enjoyed hearing about Dr. Goldring’s collaboration with Dr. Bishop and his influence on him, which highlights the interdisciplinary nature of neuroscience. Furthermore, regarding the field of psychiatry, I was surprised to learn that WashU was one of the few academic centers that was not dominated by psychoanalysis. I admire Dr. Robin's significant contributions and influences on direction of psychiatric research and diagnostic criteria. Finally, I particularly enjoyed Dr. Landau’s anecdotes, recollections, and personal memories regarding Drs. Schwartz, Goldring, O’Leary, Berg, and Sachs. While the theme of today’s lecture focused on neurosurgery, neurology, and psychiatry, it also focused on those who would eventually start and develop neuroscience related fields at Washington University. Much of the session focused on researchers who pioneered evidence–based methods in the study of psychiatric disorders, neuroscience, and neurosurgery which had not been studied well. This was especially important in the field of psychiatry in a time when the philosophy of psychoanalysis pervaded the field. Another main point of today’s session was the importance of mentorship in the field of research. Many of the people discussed today took a particular interest in teaching and would be mentors for many of the prominent researchers and clinicians in the field today. Today’s discussion revealed the importance of the people in the process of research and how the movement of researchers could greatly influence the productivity of a department.



I was interested in the intersection between basic science and neuroimaging with the somewhat more qualitative field of psychiatry. My primary background has been in neural signal processing and imaging as an approach to ontological study, generally not covering the more large-‐scale studies of cognition and neural function. Combining the basic science and philosophical approaches seems to be an interesting method of gaining more knowledge about cognition. In our discussions, I find the area of university/academic politics very interesting, as well as the circuitous routes that academics take through their careers to various universities. The development of evidence-‐based psychiatry is especially interesting in how it was able to combat the faith-‐based beliefs in mental illness. For today’s session, we learned about the development of neurosurgery, neurology and psychiatry. It was interesting to see how psychiatry evolved from being a domain completely separate from neurology and neurosurgery (psychiatry was dominated by psychoanalysis; neurology and neurosurgery had nothing to do with psychoanalysis) into a field that was highly informed by findings in neurology and neurosurgery. It was also eye-‐opening to learn about how different the training process was for physicians back in the day, and a little bit upsetting to learn that almost everyone we read about today graduated from medical school at or before the age of 21! Finally, I found to be of historical interest, the intricacies of how faculty positions were structured and funded, and how faculty funded their positions back when institutional funding for faculty positions was scarce. I enjoyed learning about Eli Robins’ work in evidence-‐based evaluation of psychiatric disorders such as suicide and depression. It was interesting hearing about this pivotal change in psychiatry. I also appreciated Dr. Lindau's thoughts and anecdotes on his colleagues. I also enjoyed reading about George Bartelmez's transitional studies from zoology to neurohistology that were all based on his versatile expertise with the light microscope.



This week’s readings were extremely interesting to me because of my interest in pursuing a career in psychiatry. Incidentally, one of the readings from this week’s selections addresses a question that was brought up to me when I was applying to medical school. I studied psychology in New York City as an undergraduate. Studying psychology gave me the vision of my potential psychiatry practice being a perfect blend of “doctoring,” by prescribing medicine, and psychotherapy. Additionally, New York is one of the last havens for Psychoanalytic thought, which had a large impact on my experiences with the field. Therefore, when applying to medical school, I was warned about Washington University, being told that it focused too much on the biological and biochemical aspects of psychiatric illnesses, and ignored the psychological components of mental illness. It is quite surprising that Guze wrote about this topic in this 1989, yet the exact same critique of the school still exists 15 years later. Indeed, it is actually quite confusing that this exists. During my undergraduate career, every single psychology class that I took made sure to emphasize the medical model of classification, research, and treatment of mental illnesses. It is confusing that individuals could champion the developments of the faculty of Wash U, including the diagnostic system; yet condemn the school for focusing too much on science and biology. Especially while much of the field of psychology moves closer to the medical model. It seems that even more understanding of the brain is required.



Session IV. Wednesday April 30 -‐Radiology, CID*, and IBC†

*Central Institute for the Deaf -‐ now in the Department of Otorhinolaryngology †Institute for Biomedical Computing – now in the School of Engineering

Focus: Advancing technology and analysis of the structure and function of the nervous

system. [Rollovers from 4/23/2013] Ms. Lin Schwartz HG, and O’Leary JL. 1941. Section of the spinothalamic tract

in the medulla with observations on the pathway for pain. Surgery 9:183-193.

Ms. Gartland Robins E, Guze SB. 1970. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiat 126: 983-987.

Mr. Donahue Guze SB. 1989. Biological psychiatry: is there any other kind? Psychol Med 19:315-323.

Summarizers: Mr. Lalezari Woolsey TA. 2000. Rafael Lorente de Nó, 1902-1990. Biogr Mem Natl

Acad Sci. 79:85-105. Mr. Tobias Galambos R. 1998. Hallowell Davis, 1896-1992. Biogr Mem Natl Acad

Sci. pp. 1-23. Ms. Tang Galambos R, Davis H. 1943. The response of single auditory-nerve

fibers to acoustic stimulation. J Neurophysiol 6:39-57.



Mr. Rogalski -----------. 2002. Charles E. Molnar – 14 March 1935 – 13 December

1996. [http://www.cse.wustl.edu/history/molnar_c/molnar.html] -----------. 2013. Charles Molnar.

[http://en.wikipedia.org/wiki/Charles_Molnar] Mr. D’Amelio Clark WA, Molnar CE. 1964. The LINC: a description of the laboratory

instrument computer. Ann N Y Acad Sci 115:653-668. Ms. Aum Kunkler V. 1996. Michel M. Ter-Pogossian (1925-1996). Focal Spot.

Vol 27. [http://beckerexhibits.wustl.edu/mig/bios/terpogossian.html]

Mr. Arriaga Ter-Pogossian M, Raichle ME, Sobel BE. 1980. Positron-emission tomography. Scientific American 243:170-181.

Other references for voluntary consideration: Kim DK, Molnar CE, Pfeiffer RR. 1973. A system of nonlinear differential equations modeling

basilar-membrane motion. J Acoust Soc Am 54:1517-1529. Lorente de Nó R. 1943. Cerebral cortex: architecture, intracortical connections, motor

projections. Chapter XV. In: JF Fulton, Physiology of the Nervous System. Oxford: New York, pp. 274-313.



Session IV -‐ April 30, 2014

Faculty: Drs. Price & Woolsey

Now that biological bases for psychiatric disorders are generally well-‐accepted, it’s hard to imagine a time when someone would have told Dr. Guze that the psychiatry residency at WashU was too focused on biology. I liked Guze’s comparison of psychiatric disorders to cardiovascular conditions – something with a biological basis that can be environmentally triggered. Deep-‐brain stimulation for treatment of depression is something I heard about in undergrad, so it was interesting to hear Dr. Price talk about that (and the research that led to its implementation). Conversely, I had never heard of audioanalgesia, probably precisely because Davis’s research showing that it could lead to permanent hearing loss led to its disuse, so that was interesting for the opposite reason – usually we don’t talk about treatments that didn’t work out.

My favorite one-‐liner from this session: “Computers don’t save time, they merely redistribute it” from Dr. Molnar. In the first part of today’s discussion, I thought the amount of personal information and detail in Angela’s article was unexpected – I don’t see that happening in modern-‐day papers about the spinothalamic tract. It is incredible that the doctors were able to create pain-‐free life without a full knowledge of the pain and physiological pathways. Although the Robins and Guze article that I reviewed was specifically about schizophrenia, it was great to see the psychiatric application work of WashU being applied to studies done throughout the world. People don’t think about everyday technology like Internet and computers being developed from medical/scientific laboratories. I never knew contributions from WUSM scientists would have had such influence over everyday life, not just medical issues. I also thought it was funny how difficult it was for us to understand the technical descriptions of the LINC – it used such old technology and parts that its hard for us, on our MacBooks and touch screens, to conceptualize.



Today we finished our discussion of the diagnosis and treatment of psychiatric disorders and neurological disorders with psychiatry, neurology, and neurosurgery. What was most interesting was realizing that the predominant approach to psychiatry at the time did not give much thought to the biological basis of neurological/psychiatric disorders. It was interesting to see how research in this realm was slowly able to change the minds of researchers at other universities who originally gave little heed to biological psychiatry.

The rest of today’s readings focused on the development of instruments that improved research techniques in the advancement of neuroscience. One interesting discovery was how they found that the cochlea was an active process and not a passive process as was originally thought. We also talked about the initial application of computers to research that was limited in its initial ability and started off as not being very user friendly. Increases in processing powers of computers would eventually allow the development of machines such as the PET scan, greatly improving the ability of researchers to visualize the inner body.

I found Dr. Schwartz’s idea to attempt a lesion of the spinothalamic tract in the medulla to cure intractable pain interesting and brave. The surgery showed that afferent pain fibers run in the spinothalamic tract and helped to elucidate the organization of the pathway. I found Dr. Guze’s work particularly fascinating and surprising especially the fact that as late as the 1980s psychiatry was not universally considered to have a biological basis. I think it was wise of him to emphasize biology in the field of psychiatry and agree that biological therapy of psychiatric illness and psychotherapy can complement each other and coexist. I was also interested in the short-lived rise and fall of audio analgesia. I had never heard of the procedure and was surprised that it could be done. I recognize why Dr. Hallowell Davis would be concerned that it could cause deafness in patients and I agree with him that its use should have been discontinued but I would really like to learn more how it works. Overall, I found today’s session fascinating and enjoyed learning about how these various personalities played major roles in developing the technologies we take for granted today: the lab computer, EEG and PET.



Today’s session was about advancing technology and analysis of the structure and function of the nervous system. I enjoyed hearing stories about the colorful characters who were responsible for the technological advancements that drove biomedical research in the past half century. It was also interesting to learn about when and how the developments that brought computers into common usage happened. Learning about the state of technology when many of the most fundamental discoveries of neuroscience happened also made me appreciate the constraints that researchers of that time were operating under, as well as the ingenuity of researchers in working around the technological limitations of their time. Today’s session focused on the various faculty members who engaged in pioneering work in the structure and function of the nervous system as well as technological advances and neuroimaging. I had the opportunity to read an article by Drs. Galambos and Davis describing the behavior of single auditory nerves in response to auditory stimulation. Impressively, this experiment was also the first evidence of single neuron recordings from the CNS. Dr. Davis, along with Dr. Lorente de Nó, were on the forefront of research on the auditory system and worked at the CID here in St. Louis. Furthermore, I learned about Dr. Molnar’s work in developing the LINC, which was the first microcomputer and the forerunner to the personal computer. What I found remarkable during today’s session was how so many of the common and integral technologies we use today in the medical field, such as the PET scan, were pioneered right here at this institution. Today’s session was very exciting in that it weaved in superbly with the information that we are currently learning in our neural sciences course. I had just been studying the vestibulo-‐occular pathway last night, and then read the biography of the man who spent much of his life describing it. This course in general has really been expanding the facets of science in my learning. I especially liked today’s discussion about the first personal computer. A device that I knowingly take for granted had such a rich and vibrant history.



It was very nice how the spinothalamic transection operations markedly reduced pain from lower extremities as intended. However, it is unfortunate that both patients died shortly after their operations due to their primary illnesses. I was very interested in the paper by Guze, head of the Psychiatry Dept. at Wash U and his view on the biological component of psychiatry. I agreed with him on many points such as how brain functions reflect the results of biological evolution and selection and Psychopathology is the manifestation of effects on biological processes. There is indeed a very strong and innate derivation of brain function from the genome and interactions with environment. It was nice hearing about Rafael Lorente de Nó who seems like a very vivacious scientist. I was impressed by the extensive and also comprehensive work he did on nerve physiology as well as neurophysiology ranging from the cerebral cortex to synapses. It was also great to hear about the major figures behind the technical components that are so helpful and even necessary to biological research. Molnar's work on personal computers and circuit design made dramatic changes to research since biological researchers now had efficient and effective computer tools. It was also nice hearing about the development of the PET scan led by Ter-‐Pogossian. It was interesting hearing about the mechanism by which it works from isotope tagged molecules to looking at the densities of gamma ray emitting molecules to looking at blood flow and metabolism in the heart. It was also nice hearing Dr. Price's input on the limitations of PET scans in the brain as they depend on the relatively slow clearance of Glucose uptake. Before I get into the meat of today’s topics, I would like to comment on a residual topic from last time. It was very interesting to see the discussions on the physiological basis of psychiatric disease through Dr. Guze’s work. I found it incredible that as recent as 1989, people argued against the validity of a biological basis to psychiatric disease. This seems like a cornerstone of modern psychiatric medicine and to think that 20 years ago it was still an idea up for debate speaks to the explosive growth of the field in part due to new technologies which leads me to today. I believe that today’s discussion of the pioneers really emphasizes medicine’s growing interconnection with and dependence on technology. Molnar and Ter-‐Pogossian revolutionized medicine with their discoveries of the LINC and PET scanner respectively. It is hard to imagine modern research succeeding without the personal computer and a whole field of cancer imaging resulted from the PET scanner. I think that the marriage of medicine and technology will not only stay the course but will flourish even more in the coming years.



Examining the technologically that was originally used in neuroscience and comparing it to modern day technology is quite amazing. It seems that the early days of neuroscience were limited by the lack of powerful, fast, and sizable computers and other instruments. Additionally, clearer and more accurate imaging was continually a desire. The LINC computer and PET imaging techniques were some of the early ancestors of our modern technology and solved some of these problems. However, it is extremely interesting to see how, as technology has progressed, allowing us a better picture of what is going on in the nervous system, we still require greater resolution in our imaging and stronger, faster computers. Additionally, although we have discovered quite a bit since the early days of neuroscience, it is mind-‐blowing how much is still unclear, and how much we still have no idea about. Even though we have technology that was probably not imaginable to some of the people we have talked about, we are still extremely far from understanding much. As an engineer, I always find the juxtaposition of engineering and medicine fascinating. It's interesting how concepts used for other purposes (radar, etc.) can be applied to different fields. I enjoyed the discussions about the development of the LINC, as I wasn't aware of its background. The initial discussions about the biological basis of psychiatry surprised me in how long it took the medical community to accept what is now a rather obvious idea. I was most interested in the work by Galambos and Davis on the response of single auditory neurons. The accurate response of each neuron to a preferred frequency was instrumental is understanding auditory encoding and the future development of cochlear implants. This preference is especially interesting considering the origins of cochlear implants as single electrode stimulators which according to even the modern canon of tonotopic response of cochlear ganglion cells should never have functioned. It seems possible that at frequency levels at which phase locking remains possible that even coarse single electrode stimulation will stimulate the proper frequency neuron. It would be interesting to see a related study comparing the response of these fibers to local electrical stimulation as opposed to the acoustic stimulation used here.



Session V. Wednesday May 7 -‐ The Neuroscience Program

Focus: Integration of neuroantomy, neurophysiology and other disciplines into

neuroscience. Summarizers: Ms. Angela Lin Hunt CC. 2006. Carlton C. Hunt. The History of Neuroscience in

Autobiogaphy. Volume 5. pp. 352-380. Mr. Lalezari Hunt CC, Kuffler SW. 1951. Stretch receptor discharges during muscle

contraction. J Physiol 113:298-315. Mr. Ko Hunt CC. 1955. Monosynaptic reflex response of spinal motoneurons to

graded afferent stimulation. J Gen Physiol 38:813-852. Ms. Gartland Hunt CC. (1990) Mammalian muscle spindles: Peripheral mechanisms.

Physiol Rev 70: 643-663. Mr. Donahue Cowan WM , (Stanfield B). 2004. William Maxwell (Max) Cowan. The

History of Neuroscience in Autobiogaphy. Volume 4. 146-208. Mr. D’Amelio Cowan WM, Powell TPS. 1954. An experimental study of the relation

between the medial mammillary nucleus and the cingulate cortex. Proc R Soc Lond Ser B

Ms. Aum Cowan WM, Gottlieb DI, Hendrickson AE, Price JL, Woolsey TA. 1972. The autoradiographic demonstration of axonal connections in the central nervous system. Brain Res 37:21-51.

Mr. Arriaga Cowan WM. 1979. The development of the brain. Scientific American 241:113-133.

Other references for voluntary consideration: Kuffler SW, Hunt CC, Quilliam JP. 1951. Function of medullated small nerve fibers in

mammalian ventral roots: Effect muscle spindle innervation. J Neurophysiol 14:29-54. Hunt CC, Kuffler SW. 1951. Further study of efferent small nerve fibers to mammalian muscle

spindles: multiple spindle innervation and activation during contraction. J Physiol



113:283-297.

Hunt CC, Wilkinson RS, Fukami Y. 1978. Ionic basis of the receptor potential in primary endings of mammalian muscle spindles. J Gen Physiol 302:683-698.

Van Essen DC, Price JL. 2002. Obituary: W. Maxwell Cowan (1931-2002). Nature 418:600. Wann DF, Woolsey TA, Dierker ML, Cowan WM. 1973. An on-line digital computer system for

the semi-automatic analysis of Golgi-impregnated neurons. IEEE Trans Biomed Eng BME 20:233-247.

Wann DF, Price JL, Cowan WM, Agulnek MA. 1974. An automated system for counting silver grains in autoradiographs. Brain Res 81:31-58.



Session V -‐ May 7, 2014

Faculty: Drs. Landau, Price & Woolsey

I enjoyed learning about Dr. Hunt’s endeavors in studying muscle spindles and motor responses. It was interesting to hear about his experimental method of exposing the muscles of a cat, severing the innervation, and then stimulating the dorsal and ventral nerves at varying degrees. I was particularly interested in learning about the development of autoradiography to visualize axonal connections along with its advantages and limitations. I appreciated learning about the physiologic mechanisms underlying this visualization technique and how it differed from the pre-‐existing neuronal degeneration visualization techniques that are dependent on pathologically induced mechanisms. It was also interesting to hear about Dr. Cowan’s summary of Sperry’s 1963 experiment on reversing the frog’s visual perception by 180º by rotating an eye that regenerated original neuronal connections after the frog had completed its neural development. I also enjoyed hearing about Dr. Woolsey’s research on barrel cells that are involved in the innervation of mouse whiskers and how he observed their plasticity after whisker removal.



I am very glad that I chose to do this selective, as it has exceeded my expectations of what I thought I would gain from it. Before taking this selective, I took the facts that I learned in class for granted, thinking that they had been discovered by ‘someone’, ‘somewhere’. Learning about all the groundbreaking work that was done on this campus has given me a new appreciation for the institution that I am attending, and a new respect for the research that takes place here. I also appreciated the selection of articles, and the inclusion of autobiographies, biographies, as well as eulogies into the mix. I have always enjoyed reading books on the history of science and medicine, and I feel that this selective, through its diverse selection of reading materials, as well as the anecdotes of Drs. Landau and Price, gave me the privilege of learning about a period of development in neuroscience that has yet to be comprehensively chronicled in an easily-‐accessible tome. The effort to learn about the scientists we discussed, not just as researchers, but also as humans who possess foibles, failings, and idiosyncrasies has made the study of neuroscience a lot more colorful for me. I was struck by how much of the pioneering neuroscience work at WashU was done in contravention of the conventional wisdom of that time (e.g. Eli Robins’ work in WashU’s department of psychiatry). Perhaps WashU’s location in the Midwest—a comfortable distance away from the spheres of influence of the East Coast and West Coast schools—facilitated that. Perhaps like attracts like, and a founding population of outsiders at WashU attracted like-‐minded outsiders willing to challenge the received dogma of their time. In any case, I hope that WashU continues to lead the charge in advancing the field of neuroscience, whether in mapping the Human Connectome or in elucidating the genetics of neurological disorders. Thanks for making this an enjoyable selective.



Washington University is currently one of the top cutting-‐edge neuroscience research centers of the world. This class showed me that although the modern-‐day technology wasn’t around yet, WashU has been as cutting-‐edge a neuroscience center as possible for any time period for many years. The scientists that we discussed in class were all leading their fields using any and all available technology and resources. I think this resourcefulness was and remains a key attribute for leading a field like neuroscience in research. In particular, the articles I read by Hunt, Guze, and Robins showed the drive of WUSM neuroscientists to keep pushing the boundaries of what has been accepted. Guze and Robins, for example, recognized that the classification of psychiatric disorders was not good enough, so they strove to create a better and more accurate method of diagnosis. Hunt acknowledged that muscle spindles were well understood, yet still compiled the available information and called attention to the research yet to be done on the topic. Others were stalled by lack of resources or tools, but made do with what was available and churned out groundbreaking research. This drive for exceeding expectations seems to me to be the most important factor in pushing WUSM to the top of neuroscience research. The future of neuroscience is promising for WashU. The involvement of the neuroscience pioneers in teaching current students, like in this class, and shaping their research careers means many of us will stay at WashU throughout our careers. As this class has taught us, WashU is a place where people of all backgrounds and ambitions can come to conduct research, allowing growth and diversity for past and future discoveries.



So many facts that we students now take as given—classifications of different kinds of peripheral nerve fibers, the role of the spinothalamic tract in pain sensation, the form and function of muscle spindles—were discovered in living memory here at WashU. Even the idea of psychiatry as a biologically-‐based discipline and medical specialty, which I have taken for granted my whole life, was shaped by the vision of WashU neuroscientists. More recently, the Human Connectome Project is the current face of neuroscience in popular culture, and of course it is based at WashU.

A consistent theme in the biographies of the WUSM/WUSTL pioneers in neuroscience is the sense that they found a supportive academic home at WashU. Dr. Hunt said he “[felt] fortunate to have started out in neuroscience when it was a small and friendly enterprise—and at a time when the field was undergoing an exciting intellectual transformation.” While the neuroscience community has increased in size by orders of magnitude, and though today’s technology is a far cry from the homemade CRTs used by Bishop, Erlanger, and Gasser, the collaborative, interdisciplinary environment at WashU and the close relationship between advances in neuroscience and advances in technology continue to keep the field in a state of “exciting intellectual transformation.”

Many of my classmates (including several in this selective) have professional interests in neuroscience, neurosurgery, or psychiatry, and I look forward to hearing about their accomplishments in this field. I look forward to the day when the Human Connectome Project is declared complete, and I fully expect connectome mapping to become as ubiquitous within my lifetime as genome mapping has already become.



At the dawn of the twentieth century, Neuroscience was a rudimentary scientific discipline split up among disparate academic departments and medical specialties. By the dawn of the twenty-first, it had progressed substantially beyond its very basic beginnings by developing its own methods and journals and forging its own departments at centers of biomedical research all around the world. As it turns out, many of the pioneers of Neuroscience who helped establish some of the main principles and methods did much of their major research right here at Washington University. These pioneers in Neuroscience were always pushing the limits of the rapidly advancing technology of the twentieth century. In the 1920s, Drs. Erlanger, Gasser and Bishop came together at Washington University to work on developing newly invented cathode ray tubes into a useful machine for recording nerve impulses. Others of these pioneers were instrumental in developing such staples of the field as PET, EEG and axonal tracing methods. Meanwhile, others’ findings fundamentally changed biology such as when Drs. Levi-Montalcini, Hamburger and Cohen identified the nerve growth factor. And, some of their contributions completely revolutionized, or even were instrumental in developing, other related fields. For example, Dr. Guze emphasized the biological aspects of psychiatry, which until the late 1980s was still not fully accepted among the fields. And, Dr. Davis was instrumental in developing the field of audiology, in part by studying the pathways of audition from cochlea to cortex, and developing standard methods for hearing tests, including those used to test hearing in infants. The contributions of these great scientists to developing a comprehensive and burgeoning discipline cannot be overstated and their findings have made huge differences in our understanding of the workings of the human nervous system. While many of these researchers made important individual contributions in their day toward understanding the nervous system, each had his or her own appointment in another department. They were physiologists, biochemists, and anatomists, etc., who happened to have an affinity for the nervous system. However, because of their contributions to expanding the nascent field of neuroscience, these researchers enabled Dr. Cowan, to create a department of anatomy and neurobiology to bring together the disparate researchers of the field and give them a single home. This revolution in thinking about neuroscientific problems helped train a new generation of researchers with access to a wealth of methods that were specific for solving the problems of understanding nervous tissue and was responsible for the creation of the integrated neuroscience course that I, as a first-year medical student, enjoy today. It is easy to take for granted the understanding of the human nervous system and learning about these people and their contributions to the field have shown me the meaning of the statement attributed to Issac Newton, that, “If I have seen so far it is only by standing on the shoulders of giants.”



This course showed us how pioneers at WUSM contributed to the field of neuroscience throughout the last century. It was exciting to be able to go through the brief history of neuroscience as a field in only a few short weeks and to see how influential Washington University was to the advancement of it. One aspect that stuck with me was how neuroscience advancements mirrored the evolution of technology. We went from the beginning of the 20th century, which included Ramón y Cajal and his histological drawings to the present day with the advent of advanced neuroimaging techniques like fMRI. I believe that neuroscience unlike any other field is tied inexplicably with technology. Along those lines, it was extremely impressive what the researchers were able to accomplish with the technology they had at hand. I found it fascinating that they were able to use cathode ray tubes, which was brand new technology at the time, to measure electrical nerve impulses and thus prove their existence. One aspect of the class that I really enjoyed but didn’t expect was the context and perspective the course provided to the scientific advancements we learn about everyday in our neuroscience classes. We take for granted much of the work that went in to what we now consider to be facts. For instance, we learned the importance of nerve growth factor in class but we didn’t know that much of the work that went into discovering NGF came from work in a home laboratory that existed because Rita Levi-‐Montalcini was being persecuted for being Jewish. It must have taken incredible courage to continue working on NGF while her life was continuously at stake. It is these anecdotes that I really enjoyed learning about throughout this course. Lastly, it was easy to be impressed by the numerous advancements made in neuroscience here at Washington University. It is clear that we are a powerhouse when it comes to neuroscience research. However, I thought it was equally impressive how much time and effort much of the faculty like Dr. Schwartz and Dr. Goldring committed to the teaching of future clinicians. If I remember correctly, it was around half of the neurosurgery residents that Dr. Schwartz had taught who went on to be program directors at other schools. That is incredible! I think it really speaks to the positive environment that Washington University provided to researchers and clinicians. There were many times during our discussion that Dr. Landau produced anecdotes that spoke to WashU’s commitment to creating an institution that fostered innovation and trained future leaders. I am proud to be a part of this school’s rich tradition in learning and teaching.



This course provided me with a perspective on research and discovery that I likely would not have gotten from traditional classroom learning in medical schools. One of the main points that stuck out to me was the major component of personal interactions that effect how research is conducted and progresses. In the session about psychiatry and those scientists who pioneered methods and validation of longitudinal studies, it was mentioned that when a researcher left Washington University, the entire program drastically decreased in productivity for three years. The first session on the initial discovery of different afferent fibers also showed that having the right combination of people collaborating at the same institution could lead to great discoveries. This made me realize the importance of the environment and finding the right mix of people in research.

I was also surprised about the struggles that those at Washington University had in starting and maintaining the neuroscience program. While I knew that certain specialties like emergency medicine arose relatively recently, neuroscience seemed to be a topic that would have been around forever. It was interesting to look more closely at the beginnings of a new field when it was not as entrenched in people’s minds. This was highlighted when those at Washington University were mocked for having a more biological view of psychiatry and neurology rather than the prevailing view of the time.

Lastly, I greatly enjoyed gaining some insight to the personal lives of those who made great strides in their field. Often, in the classroom, the discoveries made by researchers are presented quickly and with such finality that it is easy to forget the struggles and endless amounts of work it took to make one minute of a presentation. Having had these discussions, I believe I will have a greater appreciation of not only of the work of researchers but the many factors, both personal and environmental, that impact discovery.



With the tremendous amount of discoveries and advancements in neuroscience, it’s hard to believe much of the development took place not too long ago. It was a great opportunity to be able to read the first published findings of many of the facts we learn in our neuroscience course today. Many of these discoveries seem so well established and accepted, which is why I find it hard to believe they were made within the past few decades. Learning about the different pioneers and the various fields they worked in allowed me to gain an appreciation for the interdisciplinary nature of neuroscience, encompassing work in psychiatry, neurology, electrophysiology, and other disciplines.

In the first session we learned about Erlanger, Gasser, and Bishop’s work on the electrophysiology of neurons. Session II focused on the WUSM faculty involved in the isolation of NGF. Learning about how Levi-‐Montalcini built an in-‐home laboratory when she wasn’t allowed to pursue her career made me contemplate the hardships and difficulties faced by many researchers in their native countries. The third session focused on the development of the fields of neurosurgery, psychiatry, and neurology. What left the biggest impression on me from this session was Robins’ leadership in changing the direction of psychiatry and WUSM faculty’s medical model approach to psychiatry at a time when psychoanalysis dominated. In the fourth session we focused on work regarding the structure and function of the nervous systems and technological advances, including Galambos and Davis’s description of single neuron behavior and Molnar’s work on development of the LINC.

As I mentioned in a previous summary, I continue to be astonished by the dedication of these faculty to their work. Their passion and commitment to developing and advancing the field of neuroscience provides a basis for and allows much of the research that takes place today to be possible. Reading the memoirs and biographies on the faculty gave me a sense of who they were as a people in addition to their contributions to neuroscience. The many anecdotes provided by the faculty leading this selective also gave these sessions a personal touch, which I greatly appreciated and enjoyed.

Thank you for leading such a great selective, I really enjoyed it!



This selective has been interesting because it put the developments in neuroscience into a real life context. Over the past several weeks, our neuroscience course has been in full swing. We hear many lectures about things such as muscle spindles, nerve growth, PET scanners, etc. In most of the cases these lectures are full of small details and minutia that seem like random historical points. These are frustrating because they seem like small details that make studying for the exam more difficult. However, over the last five weeks, this selective has made me understand why those frustrating details matter. During our first year of medical school we have heard numerous lectures on a huge variety of topics. It becomes very easy to learn the science and mechanisms behind medicine and ignore the fact that real people discovered these concepts. During histology we learned about muscle spindles, which we are learning more about in neuroscience right now. This seemed like just a group of muscles with some function that I needed to know to pass an exam. However, now I realize this was something that a person slaved over in order to find out the mechanisms behind its function. The scientific world is not as cut and dry as it seems in most instances. Politics, friendships, controversies, and rivalries litter all of the breakthrough discoveries in the neurosciences. However, the most important part of this selective was not necessarily the specifics of the people we learned about. Rather, I think that the most important thing I took away from this selective was to approach the research I learn about in all of the other fields with the knowledge I gained from this class. I think I will have a better understanding of the humanity that is attached to all of the discoveries in the scientific world. Looking at specific aspects of the course, I think learning about the LINC computer and psychiatry was the most interesting. Again, I believe in a lot of cases we now take for granted the tools that are available. When many of these discoveries were being worked on, the computing power was not there. However, this did not stop the researchers at Wash U. Rather, they used the technology that they had, and invented new ways of doing things in order to get their research done with the underpowered machines that were available to them. Additionally, the advancements in psychiatry were extremely interesting to me. Since psychiatry is still in many cases viewed as less “scientific” or “medical” than other scientific and medical disciplines, it was interesting to see how people here at Wash U strived to make psychiatric research and diagnostics reliable and valid. In general, reading about the people who made the changes and discoveries in the neuroscience field has made things more real life, and will change the way that I think about research that is presented to me in the future.



The most important aspect of this course was the reminder that our faculty and researchers have made many great accomplishments. Having worked with connectivity data derived from retrograde tracers for some time, I took for granted the amount of work that had gone into even realizing the method as a possibility. To then realize that a number of you were instrumental in its beginnings was surprising. As I work toward my PhD, it is nice to know that every researcher's path has been long and contained many false starts between their ultimate successes. It is very easy to read through a textbook and not realize that a simple paragraph of facts could be a result of years of work. Overall, it makes me very proud to be a part of this institution, and to be among such talented and successful physicians and scientists. The history I've learned through the course has made me more invigorated to strive to add to the list of great achievements that have been made here. I thoroughly enjoyed the readings and discussions that I participated in during Pioneers in Neuroscience. It was enlightening to be able to place faces and personalities on the discoveries that we so casually gloss over in lecture. As I described in class, I don’t believe I will ever be able to read a textbook or study for a class in the same way again. Each and every molecule or innovation that I come across will inspire my mind to conjure a possible story, a possible interaction, that led to its discovery. Furthermore, the class inspired me. I look around my class and wonder what each of my classmates will bring to the world of medicine. I find myself longing more to contribute to the furthering of science. I once had the honor of sitting with Nobel laureate James Watson, and he told me never to be the smartest person in the room. I have always appreciated that advice and being here at Washington University has allowed me to hold true to it.



WUSM has had a profound impact on neuroscience throughout the past century, with discoveries in such diverse fields as electrophysiology, chemistry, psychiatry, and radiology. The discoveries in these fields revealed new avenues of inquiry that are still being actively pursued in labs across the country. The early work of Bishop and Erlanger on electrophysiological recordings of the action potential has been advanced to the multi-‐electrode intracortical arrays currently used in brain-‐machine interface research. Taking the activity of collections neurons allows us to begin to interrogate the neuronal basis of encoded thoughts and intentions. Ter-‐Pogossian's pioneering work with PET allowed a window into the same question at the opposite end of the scale. Being able to look at the activity of the living brain brought information about the function of the brain that was only available from post-‐mortem lesion studies previously. Similarly, the work of Hamburger, Cohen, and Levi-‐Montalcini on NGF revolutionized our understanding of neural development and growth. NGF and other neurotrophins are active fields of investigation today and have been implicated in many neurological diseases and identified as future therapies for nerve and brain injuries. Additionally, Dr. Guze’s focus on the biological bases of psychiatric phenomenon was a bold move contrary to the standards of other departments around the country. This firm belief in the neurobiology as a foundation for diagnosing and treating disease has been validated numerous times over the decades.



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Facit 5-‐15-‐2014