Abstract
Born in San Francisco in 1874 into the family of German immigrants in which he was the only one to proceed beyond elementary education, Joseph Erlanger graduated from the University of California (Berkeley) in 1894. He was about to enter the local Cooper Medical School when he was told that the new medical school in Johns Hopkins University (Baltimore) aimed to surpass all others, and there he graduated and was later coached for a career in academic life by William H Howell (1860–1945). In due course he held the Chairs of Physiology in the University of Wisconsin (Madison) and Washington University at St Louis, Missouri. He showed that the Bundle of His is indeed the functional link between the atria and the ventricles in the mammalian heart and that the Korotkoff sounds are produced by a ‘breaker’ phenomenon resulting from instability of the pulse wave in a partially occluded artery. With Herbert S Gasser (1888–1963) he was awarded the Nobel Prize in 1944 for their work on action currents in peripheral nerve fibres. The history of science occupied him during his retirement. He died at St Louis in 1965.
Introduction
The transformation of medical knowledge during the nineteenth century insensibly led on to alterations of the medical profession and the training of its practitioners. Medical schools flourished in the ever-expanding United States of America but the education provided in them varied widely in quality and value. 1 It is probably true to say that the professionalisation of medical practice began in the newly-founded Johns Hopkins Medical School in 1884 which was destined to excite widespread emulation. 2
Milestones
Among the huddled masses who streamed through the golden door of New York Harbour in 1842 was a 16-year-old youth from the village of Buchau am Federsee in Württemberg. Earlier arrivals outfitted him with merchandise and sent him to New Orleans to work as an itinerant peddler. When gold was discovered in the Sacramento Valley in California in 1847 he went west – via Panama – to San Francisco where he settled, having discovered that mining was not the surest way to earn a steady living. In 1863 he married Sarah Galinger, the sister of a fellow-immigrant and business partner. The sixth of their seven children, born to them on 5 January 1874, was the only one who took his mother’s advice to proceed beyond elementary education. Joseph took the ‘classical’ course when he went to San Francisco Boys’ High School (which also enrolled girls) and after two years enrolled in the College of Chemistry in the University of California (at Berkeley) in 1891.
Three years later Joseph Erlanger (Figure 1) began the study of medicine at the newly founded Johns Hopkins Medical School. His knowledge of German, gained at home and regularised at elementary school, stood to him at Hopkins: the recommended textbooks he used were Spalteholtz’s Anatomische Atlas, Stöhr’s Histologie, Neumeister’s Physiologische Chemie, Cohnheim’s Chemie der Eiweiskorper, Hertwig’s Embryologie, Ziegler’s Pathologische Anatomie, Nothnagel and Rossbach’s Arzneimittelehre and Koenig’s Chirurgie. To von Gehuchten he turned for the Système Nerveux de l’Homme and for physiology he relied on Michael Foster’s textbook. Travel to the West was so costly that Joseph spent the long vacation in Baltimore. During the first summer he made serial histological sections of the spinal cord showing the location of the anterior horn cells innervating the rabbit’s soleus muscle (unpublished). The following year, with his old Californian friend Albion Walter Hewlett (1874–1925), he discovered that shortening of the small intestine, already carried out by William Halsted (1852–1922) on these animals, in dogs caused slight digestive disturbance except for marked impairment of fat absorption – giving him his first publication.
3
Joseph Erlanger. Reproduced with permission from the Washington University in St Louis Magazine.
Graduation
After graduating in 1899 Erlanger was appointed to one of the 12 internships at Hopkins and at the end of the year he won the coveted Fellowship in Pathology with William Henry Welch (1850–1934) – even though the professor complained that he ‘could never read his writing’. But only a few days before he was due to take up the Fellowship William Henry Howell (1860–1945) offered Joseph an Assistantship in the Department of Physiology and Welch, though inconvenienced, released him. In Howell’s department he supervised the laboratory classes and prepared the demonstrations for Howell’s lectures, before he began to lecture in his third year. In 1904 William Osler (1849–1919) called him in to see a patient with Stokes-Adams syndrome that responded to anti-syphilitic treatment.
His reputation was spreading beyond Baltimore and in 1905 he was offered the Chair of Physiology at Madison, Wisconsin. After four years the Chancellor of Washington University in St Louis invited him to join a completely reorganised medical faculty. For four years, during which a new school was built, Erlanger and the newly-appointed chiefs constituting the ‘Executive Faculty’ concerned themselves with administration and the purchase of equipment and it was already September 1914 before normal duties could be resumed - and then World War I supervened. The explanation of the Korotkoff sounds heard over a partially obstructed artery exercised his attention in 1916 and, although he always looked upon himself as a ‘circulatory physiologist’, in 1921 with the Professor of Pharmacology Herbert Spencer Gasser (1888–1963) he began a prolonged investigation of the electrical signs of activity in peripheral nerves. Erlanger was one of the first American physiologists to import from Holland an Einthoven string galvanometer but its response time of 0.1 second was too slow to detect the electrical changes in nerve fibres during excitation. The cathode ray oscilloscope, of which the first account was published by Karl Ferdinand Braun (1850–1918) on 15 February 1897, has the ability to record millisecond (0.001 second) variations; Braun shared the Nobel Prize in 1909 with Gugliemo Marconi (1874–1937). 4 And so began the studies in the 1920s of the action potentials in frog sciatic nerve that culminated in the award of the Nobel Prize in 1944 jointly to Erlanger and Gasser for their discoveries regarding the highly differentiated functions of single nerve fibres.
To say that he retired in 1939 would be misleading for with the outbreak of World War II (1939–1945) he resumed his teaching duties when the younger men were called to the colours and in the evening of his days he devoted himself to the history of science, an adventure not new to him for in April 1915 when the new School at St Louis was opened he described in an elegant address ‘William Beaumont’s experiments on digestion on “old fistulous Alex” St. Martin’ and their present day value. Pre-deceased by his wife Aimée Hirstel, he died at St Louis on 5 December 1965. 5
Monuments
The demonstration in 1893 of the atrioventricular bundle by Wilhelm His Junior (1863–1934), son of his neurohistologist namesake (1831–1904), demolished the old view that the atria and ventricles were completely separated from one another by connective tissue. 6 He had shown that cutting the bundle resulted in complete, and permanent, atrioventricular block and so, when Osler asked Howell’s assistant in the Johns Hopkins physiology laboratory to see a patient with a very slow pulse, by graphic recording of the heart beat Erlanger showed that the condition was explained by atrioventricular block and that the patient’s fainting spells during the Stokes-Adams attacks usually occurred when partial block temporarily became complete. Erlanger devised a ‘clamp that could reversibly apply pressure on the bundle of His of the dog’s beating heart’ and was able to demonstrate all grades of heart block from the normal sequence to complete block, repeatedly. 7
After the Department of Physiology in Madison was finally organised and equipped, Erlanger resumed his heart block experiments in order to investigate the claim of Stanley Kent (1863–1958) in England, simultaneously but independently of His, that there were multiple atrioventricular connections in the normal mammalian heart, most of them running over the lateral aspects of the mitral and tricuspid valve rings. 8 Instead of clamping the atrioventricular bundle as he had done in Baltimore, Erlanger now crushed the bundle in dogs aseptically. In the surviving dogs the block remained complete as long as the dogs were observed. In a few experiments, after crushing the bundle, contiguous points above and below the rings were denuded of epicardium and sewn together: conduction was blocked completely and permanently. 9 Years later Kent repeated his assertions in short reports to the Physiological Society. In 1894 and 1915 committees organised by the British Association for the Advancement of Science examined the statements – if not the evidence – and concluded in favour of Kent objectively serving as Secretary on both occasions (with Charles Scott Sherrington chairing the cabal in 1915). 10
The origin of the Korotkoff sounds that make the auscultatory method of blood pressure measurement so far superior to the palpatory caught his interest in 1916. So he devised an apparatus to record movements of the arterial wall during very slow decompression of the dog’s uncut femoral artery in a glass-topped chamber beyond which the artery passed through to a fixed tubular bell of a stethoscope. The auditor/stethoscopist signalled the beginning of the sound and the final change of the sound from sharp to dull (not its disappearance), which respectively coincided with the systolic (−3 mm Hg) and diastolic pressures.11–14
The electrical signs of activity in nerve fibres had attracted the attention of physiologists for many years. While Erlanger was in Madison a youth from the small Wisconsin town of Platteville entered the medical school. Herbert Spencer Gasser (1888–1963) completed his clinical undergraduate course at Erlanger’s alma mater and in 1915 returned from Baltimore to Madison for a year, after which he rejoined Erlanger who had moved to St Louis in 1910. Gasser (Figure 2) was among the first to realise that the technical development of wireless telegraphy hastened by World War I might have application in electrophysiology and in 1921, with physicist HS Newcomer, he published an account of the action currents excited in cat phrenic nerve.
15
In this ‘application of the thermionic vacuum tube to nerve physiology’ the recording device, an Einthoven string galvanometer, was too slow in response to provide adequate records. Meanwhile Gasser learned that the Western Electric Company had made a cathode ray tube but when approached the Company refused to sell one to the St Louis laboratory and so Erlanger and Gasser ‘constructed a cathode ray tube out of a distillation flask. One pair of the deflecting plates was mounted inside the tube, and a pair of solenoids, attached outside, as in Braun’s original tube, acted at right angles to the former’.
16
The filament fused after a few sweeps but the physiologists were satisfied, and had seen enough of the ‘compound action potential’ to encourage further efforts and to persuade Western Electric to ‘lease’ the tubes to them.
16
‘Our competent mechanician constructed a motor-driven, rotating commutator that started the sweep circuit of the tube and stimulated the nerve at such a time that the resulting conducted action potential would appear on the tube; also he constructed a device that automatically numbered each photograph as it was made. At first the action potentials were recorded by holding the sensitised film against the face of the tube with the hand through several successive sweeps of the beam, a method that resulted in considerable dispersion of light.
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Herbert S Gasser. Reproduced with permission from the Washington University in St Louis Magazine.
And so began a veritable mini-industry initiated by Erlanger and Gasser’s reports.18–21 In 1921 Gasser was appointed Professor of Pharmacology at Washington University and he remained there until 1931 when he was invited to Cornell Medical School in New York City. In 1934 he was appointed Director of the Rockefeller Institute for Medical Research where he continued to work until his death in 1963 after he retired in 1953. He shared the Nobel Prize with Joseph Erlanger in 1944 ‘for their discoveries regarding the highly differentiated functions of single nerve fibres’. 9
Memorabilia
When in 1904 as a young assistant he had to demonstrate blood pressure measurement (a must), he broke the glass Mosso instrument that had just been imported from Italy and so he assembled and demonstrated a contraption of his own. The instrument was later manufactured commercially but a model ‘of superior construction’ devised by the Strasbourg Pathologist Friedrich von Recklinghausen (1833–1910) ‘entirely superseded mine’. A letter from his two brothers, who had built up a very successful importing business in Manila, asked whether he knew anything about an Erlanger sphygmomanometer that had been ordered by a local physician. ‘Not very long thereafter they asked me to join them and take charge of a line of scientific supplies and equipment. Had I done so, I would have been able to retire at middle age, as they did.’ 22
David Houston, the Chancellor, in inviting him to Washington University, named the new faculty members he hoped to appoint. Erlanger was unable to decide. ‘As Harvey Cushing [1869–1939] was the only one of the proposed faculty with whom I was well acquainted, I felt I could safely follow his course, and wrote him to that effect, but he kept putting me off until a decision had to be made – and I accepted. Just a few days later I received from Cushing a letter telling me he had accepted the professorship of surgery at Harvard. That post, evidently, was what he was waiting for.’
23
Memento and conclusion
William Howell was his mentor and model. In his early days as a demonstrator he failed with the capillary electrometer to display a nerve action potential, and the professor was happy with an action potential from a frog’s heart. 22 In writing a biographical memoir of Howell, Erlanger recalled that Howell always spoke well of Henry Newell Martin (1848–1896), his teacher, declaring ‘I owe him much; I had a very great affection for him’ and the experience of those years stood out in his memory as the golden period of his life, in spite of increasing responsibilities due to Martin’s failing health. In Martin’s laboratory ‘there was no pressure … to make a great discovery or even an important discovery’. 25
When the University of Wisconsin offered Erlanger an Associate Professorship in 1905, Howell, his chief, advised him ‘to decline the call – “if they want you”, he said, they would make a better offer’. He was right; the next year … they offered me the Professorship of Physiology and Physiological Chemistry’. Five years later, when he was parting from Chancellor Houston who had offered him the Chair in St Louis, he ‘asked him to let him have the conditions in writing (the advice my first chief had given me)’. Thirty-four years later, the Nobel Institute approved the appointment.