History of Neurology JOSEPH ERLANGER MD 1874 1965

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History of Neurology JOSEPH ERLANGER, MD (1874 – 1965) HERBERT GASSER, MD (1888 –

History of Neurology JOSEPH ERLANGER, MD (1874 – 1965) HERBERT GASSER, MD (1888 – 1963) THE WASH U “AXONOLOGISTS” AND THE CONNECTION TO THE BRITS RICHARD J. BAROHN, MD THE UNIVERSITY OF KANSAS MEDICAL CENTER

Joseph Erlanger, MD (1874 -1965) The Wash U “Axonologist” 1874 Born in San Francisco,

Joseph Erlanger, MD (1874 -1965) The Wash U “Axonologist” 1874 Born in San Francisco, CA Parents were Jewish-German immigrants 1895 BS; UC Berkley 1899 John’s Hopkins Medical School and Internship • Worked under Osler • Patented a new type of Sphygmomanometer • Assistant & Associate Professor in Physiology & worked in GI and Cardiology 1906 1 st Chair of Physiology; Univ of Wisconsin Madison Gasser was his student 1910 Moved to Wash U in St. Louis • Initial work in Cardiology then switch to Neuroscience • Influence from Gasser who wanted to record nerve action potentials 1922 Amplified action potentials of bullfrog sciatic nerve (Am J Phys) Also studied frog nerves, cat tibial nerves, & dog phrenic nerve 1921 Landmark Publication in Neuroscience

Herbert Gasser, MD (1888 -1963) The Wash U “Axonologist” • 1888 – Born: Platteville,

Herbert Gasser, MD (1888 -1963) The Wash U “Axonologist” • 1888 – Born: Platteville, WI; Father was an Austrian immigrant & physician • 1907 – University of Wisconsin for undergraduate & medical school • 1909 – Began working under Erlanger • 1913 – Transferred to John’s Hopkins to finish MD • 1916 – Went back to Univ. of Wisconsin briefly then to Washington Univ. • Break to serve in WW 1 in physiology of chemical warfare • Then Rockefeller grant fellow in London Paris and Munich-learned about new lab equipment • 1921 – Professor in Pharmacology at the age of 32 • 1931 – Professor of Phys at Cornell Medical College NYC • 1935 -1953 – 2 nd Director of the Rockefeller Institute (after Simon Flexner) • 1936 – Gasser and Erlanger gave a series of lectures at the Univ. of Penn summarizing their research into the actions of human nerve cells. • 1944 – Jointly received the Nobel Prize

Herbert Gasser, MD & Joseph Erlanger, MD Their Discoveries FIRST DISCOVERY • Increased amplification

Herbert Gasser, MD & Joseph Erlanger, MD Their Discoveries FIRST DISCOVERY • Increased amplification of nerve recordings by 2 techniques: 1. New Western Electric cathode ray tube for displaying nerve impulses oscillography defibrillator • A 3 (multistage) vacuum tube amplifier 2. Recorded actions potential of nerve trunk with greater accuracy & reproducibility & magnified nerve events up to 7, 000 times • 1921 – American Physiological Society showed plot of action potential • 1922 – A Study of the Action Current of Nerve with the Cathode Ray Oscillograph (Amer. J. Physiol. , 1922; 62: 496 -524)

Herbert Gasser, MD & Joseph Erlanger, MD Additional Discoveries • 2 nd Discovery: •

Herbert Gasser, MD & Joseph Erlanger, MD Additional Discoveries • 2 nd Discovery: • Showed actions potential was complex • Indicated conductions at diff velocities for diff nerve fibers and also that thresholds for stimulation was different • 3 rd Discovery: • Showed velocity of impulse is greater in larger fibers • 4 th Discovery: • This ultimately led to classification of fibers as 1. Type A. largest/fastest 2. Type C. unmyelinated/slowest 3. Type B intermediate • Fiber types associated w/ functions-light touch, dull & sharp pain, temp • 1944 - Nobel citation for “discoveries relating to the highly differentiated functions of nerve fibers" Amer J Physiol. 1922; 62: 496 -524)

Herbert Gasser, MD & Joseph Erlanger, MD • In early 1920’s made very primitive

Herbert Gasser, MD & Joseph Erlanger, MD • In early 1920’s made very primitive cathode ray oscillograph • Some exploded!! “ I can only compare their progress to the trek of the pioneers in oxcarts across the plains and mountains of the West. They were pioneers of electrophysiology and they encountered every kind of obstacle but the Indian. Far more time was spent of reconstruction than on recording of nerve, when one good record occasionally made a successful day. ” G. Bishop, 1966 quoted in O’Leary and S Goldring, Science and Epilepsy. New York: Raven Press, 1976, p. 150

Gasser, Erlanger, & Sir/Baron Edgar Adrian • Adrian, in Cambridge UK had studied with

Gasser, Erlanger, & Sir/Baron Edgar Adrian • Adrian, in Cambridge UK had studied with Lucas the “all-or-nothing” principle for nerve • Lucas, his mentor, died in WW 1 -airplane crash • Forbes, an American, worked with Sherrington & then Adrian/Lucas • 1919 he learned about vacuum tube amplifiers in WW 1 & showed he could multiple tiny potentials to 50 times • single-stage amplifier • Then Adrian read about Earlanger/Gasser’s multistage amp (1921 paper) & asked Gasser for instructions on how to build a new one • This allowed his lab to record from single neurons. Adrian & Zotterman - 1926 • Nobel Prize with Sherrington in 1932 when he was 43 Adrian and Zotterman 1926; Ibid. 61: p. 151.