Erlanger, Joseph
Erlanger, Joseph
(b. San Francisco, California, 5 January 1874; d. St. Louis, Missouri, 5 December 1965)
physiology.
In his late years Erlanger wrote a short but delightful autobiography in which he minimizes his scientific achievements with characteristic modesty but gives interesting details on his early family life. Erlanger’s father was born in Wurttemberg, Germany, and in 1842, at the age of sixteen, landed alone in New York, went to New Orleans, and then became an itinerant peddler along the Mississippi Valley. The gold rush drew him to California, where he became a businessman in San Francisco after having tried his luck at mining. He married the daughter of his business partner. A large family was born to them, Erlanger being their sixth child.
After two years at the San Francisco Boys’ High School—during which he acquired a sound knowledge of German and Latin—Erlanger was admitted to the University of California. He enrolled in the college of chemistry to prepare for the medical career that he already had in mind. His native abilities for observation and experimentation were demonstrated in a thesis, written in his senior year, on the development of the eggs of the newt Amblystoma.
Erlanger then attended the newly founded Johns Hopkins Medical School in Baltimore. During his medical studies he found time for research, especially during vacations, which he could not spend at home because of the cost of travel. In Lewellys Barker’s laboratory Erlanger attacked a fundamental problem of neurophysiology. In 1900 he succeeded in localizing the exact position in the spinal cord of the motor nerve cells that innervate a given muscle, by means of a delicate histological study based on the alterations undergone by the motor nerve cells of the rabbit after the excision of the corresponding muscle. Erlanger’s results were the first decisive experimental confirmation of F. Sano’s views, according to which each muscle is activated by definite motor nerve cells. Barker’s treatise “The Nervous System and Constituent Neurons” describes these findings in detail.
A year later Erlanger published his first paper, which came to the attention of William H. Howell, professor of physiology at Johns Hopkins, who, shortly after Erlanger took his medical degree, offered him an assistant professorship. In this first paper, “A Study of the Metabolism in Dogs With Shortened Small Intestines,” Erlanger sought to ascertain the extent of intestine that could safely be excised in surgical operations. This early research is marked by the dual concern for physiology and medicine with which Erlanger was always to be occupied. This is perhaps the reason why he devoted the major part of his career to the study of circulation and of cardiac physiology.
In 1904 Erlanger imagined and built with his own hands a sphygmomanometer; a form of this instrument bears his name, although others later devised similar apparatuses without mentioning Erlanger’s priority. This instrument allowed him to demonstrate that the pulse pressure can also give the precise volume of the pulse wave, a result that was to have an immediate application in the separation of the effects of the pulse pressure from those of the arterial pressure. Erlanger was thus able to demonstrate that in patients affected by albuminuria the discharge of albumin depends much more on the volume of the pulse wave than on the arterial pressure.
From 1904 on Erlanger concerned himself with the conduction of excitation in the heart. He proved that the Stokes-Adams syndrome resulted from an impaired conduction between the auricles and ventricles, similar to the effect obtained through the experimental exercise of pressure on the auriculoventricular junction of the turtle’s heart. The fainting spells that characterize the syndrome occur when the partial block of auriculoventricular conduction temporarily becomes complete. The German anatomist Wilhelm His had previously described the only conducting muscular connection between the auricles and ventricles, the narrow auriculoventricular bundle that bears his name. Erlanger devised a clamp with which controlled pressure could be reversibly applied to the His bundle of the beating heart in a dog. He thus produced all degrees of auriculoventricular block, from the normal 1:1 sequence to complete block, through the partial blocks characterized by two or more auricular beats for a simple ventricular contraction. These pioneering experiments are the basis of current knowledge of intracardiac conduction; the finer features of this conduction were to be analyzed many years later by Frank Schmitt.
In 1906 Erlanger was offered the chair of physiology at the University of Wisconsin, an assignment worthy of his abilities. Here he was asked to equip a modern laboratory, and he became responsible for the teaching of the entire field of physiology.
In 1910, when Washington University in St. Louis completely reorganized its medical school (soon to be a research center of worldwide reputation), Erlanger became its professor of physiology. New laboratories devoted to the major fundamental sciences were built close to each other in the vicinity of large hospitals, reinforced by an excellent library.
World War I diverted Erlanger’s activity to quite different problems. Among them was the treatment of wound shock, for which he proposed the administration of a solution of glucose and gum acacia, a procedure that was used successfully by the U.S. Army during its campaign in France; this was the first example of treatment by an artificial serum containing a component of large molecular weight—that is, a high polymer.
He also became interested in the problem of blind landing of airplanes. After numerous flights he proposed a new design of the instrument panel so that the major instruments would always remain in the pilot’s visual field.
As soon as the war ended, Erlanger resumed his work on circulation. He investigated the mechanism that produces the sounds of Korotkoff (the sounds that are detected by a stethoscope placed on the skin over an arterial region above which a controlled pressure is applied through a pneumatic cuff—the regular procedure for the measurement of arterial pressure). Erlanger showed that these sounds pose a difficult problem of fluid mechanics, which he solved. Working with J. C. Bramwell, he demonstrated, with an elegant and precise technique, that the crest of the pulse wave is unstable. The pulse wave breaks, as does a sea wave on a beach, because its crest dilates the artery and thus proceeds with a higher velocity than the foot of the wave. These two components of the wave can be separated by the observer as corresponding to sharp and dull sounds, respectively. When the dull sound occurs, the pressure applied in the cuff indicates exactly the diastolic pressure.
In 1921 Erlanger and his colleague Herbert Gasser, professor of pharmacology at Washington University, became associated in a new field of research. In about ten years they created, with George Bishop, modern neurophysiology with the use of the cathode-ray oscillograph (then called the Braun tube, after its inventor). Under their able hands this dim and fragile ancestor of the brilliant oscillograph of today immediately proved itself a remarkable instrument. By coupling it with amplifying vacuum tubes they obtained, for the first time, an exact picture of the action potentials that are the electric signs of the nervous impulses. Because of the smallness and brief duration of these action potentials no other instrument could record them; the cathode-ray oscillograph revealed that the nerve action potential is formed by several component waves traveling with unequal velocities. When Gasser showed these records to Louis Lapicque, the professor of physiology at the Sorbonne, Lapicque perceived their significance immediately. Ten years earlier, Lapicque and Rene Legendre had observed that nerves of slow excitability (that is, of long chronaxies) were constituted of smaller fibers than the nerves fast excitability (or brief chronaxies). Lapicque had then assumed that the impulse travels more rapidly in large fibers than in small ones. A histological investigation by Lapicque, Gasser and Henri Desoille immediately showed that multifunctional (motor and sensory) nerves that display a multiwave action potential contain two or three groups of fibers, each of which is characteristically of a different diameter. On the other hand, a unifunctional nerve—the phrenic nerve, for example—that innervates only one muscle and contains no sensory fibers is made up of fibers of uniform diameter. These results led Erlanger and Gasser to formulate their law by which nervous impulse velocity is directly proportional to fiber diameter.
Many further discoveries in neurophysiology arose from Erlanger and Gasser’s joint work. They were awarded the Nobel Prize in 1944. The disclosure of the time-course of the excitability cycle of nerve that has had a decisive impact upon all further theoretical attempts toward the formulation of excitatory processes is derived, however, from the work of Erlanger and E. A. Blair.
Although he reached retirement age Erlanger did not cease working. He resumed teaching in the medical school of Washington University during World War II, while his younger colleagues were called to military duties. He remained active after the war and was in close contact with the members of the laboratory, who benefited from his profound knowledge of all the domains of physiology. He also devoted much time to the history of this science, to the profit of the Medical School library. That he was an able and elegant historical writer is testified to by, among other things, his account of William Beaumont’s experiments, in which he interpreted Beaumont’s observations of the digestive process in the human stomach in the light of modern knowledge and showed how they constitute a most excellent experimental work a century ahead of its time.
Erlanger was a family man. In his last years he sustained with courage the losses of his devoted wife Aimee Hirstel, his only son, Herman, and his son-in-law. His reserve at first approach quickly gave way to his natural kindness and to his generous and smiling inclinations. He was an invaluable source of inspiration for both American and foreign physiologists and especially for those who had the privilege of working under his guidance in his laboratory.
BIBLIOGRAPHY
Erlanger’s works include “A Study of the Metabolism in Dogs With Shortened Small Intestines,” in American Journal of Physiology6 (1901), 1–30, written with W. Hewlett; “An Experimental Study of Blood Pressure and of Pulse Pressure in Man,” in Johns Hopkins Hospital Reports, 12 (1904), 147–378, written with D. R. Hooker; “On the Physiology of Heart-block in Mammals, With Especial Reference to the Causation of Stokes-Adams Disease,” in Journal of Experimental Medicine, 7 (1905), 675–724, and 8 (1906), 8–58; “Studies in Blood Pressure Estimations by Indirect Methods. I. The Mechanism of Oscillatory Criteria,” in American Journal of Physiology, 39 (1916), 401–466; “Studies in Blood Pressure Estimations by Indirect Methods. II. The Mechanism of the Compression Sound of Korotkoff,” ibid., 40 (1916), 82–125; “The Compound Nature of the Action Current of Nerve as Disclosed by the Cathode-ray Oscillograph,” ibid., 70 (1924), 624–666, written with H. S. Gasser; “The Action Potential Waves Transmitted Between the Sciatic Nerve and Its Spinal Roots,” ibid., 78 (1926), 574–591, written with G. H. Bishop and H. S. Gasser; “The Effects of Polarization Upon the Activity of Vertebrate Nerve,” ibid., 630–657, written with G. H. Bishop; “The Role Played by the Sizes of the Constituent Fibres of a Nerve Trunk in Determining the Form of Its Action Potential,” ibid., 80 (1927), 1522–1547, written with H. S. Gasser; “Directional Differences in the Conduction of the Impulse Through Heart Muscle and Their Possible Relation to Extra Systolic and Fibrillary Contractions,” ibid., 87 (1928), 326–347, written with F. O. Schmitt; “The Irritability Changes in Nerve in Response to Subthreshold Induction Shocks and Constant Currents,” ibid., 99 (1931), 108–155, written with E. A. Blair; “William Beaumont’s Experiments and Their Present Day Value,” in Bulletin of the St. Louis Medical Society (8 Dec. 1933), and Electrical Signs of Nervous Activity (Philadelphia, 1937).
For further details of Erlanger’s life, see his autobiographical “A Physiologist Reminisces,” the prefatory chapter to Annual Review of Physiology, 26 (1964), 1–14.
A. M. Monnier
Joseph Erlanger
Joseph Erlanger
The American physiologist Joseph Erlanger (1874-1965) made fundamental discoveries about the way in which nerve impulses are conducted.
Joseph Erlanger, the son of Herman and Sarah Erlanger, was born on Jan. 5, 1874, in San Francisco, Calif. He studied chemistry at the University of California, where he received his bachelor's degree, and then went on to Johns Hopkins University for his medical training. After he was awarded his medical degree (1899), he spent a year as a hospital resident. Between 1900 and 1906 he worked in the department of physiology at Johns Hopkins, successively holding appointments as assistant, instructor, associate, and associate professor.
In 1906 Erlanger moved to the newly established medical school at the University of Wisconsin, where he was the first professor of physiology. Shortly afterward he married Aimee Hirstel. In 1910 he became professor at Washington University, St. Louis, Mo., where he remained until his retirement in 1946.
Erlanger's early interest was in the physiology of the circulation. He studied blood pressure using a sphygmomanometer of his own devising and investigated the effect of pulse pressure on kidney function. The "Erlanger clamp" he designed reversibly to block the conduction of the auriculoventricular nerve bundle and thus was able to define some of the functions of this bundle in carrying impulses between the chambers of the heart. He also elucidated some of the mechanisms by which the flow of blood through the arteries produces sound.
In 1921 Erlanger began his collaboration with Herbert S. Gasser, investigating the properties and functions of nerve fibers. By adapting a new technique to the study of neurophysiology, Erlanger and Gasser proved the hypothesis that thick nerve fibers conduct impulses faster than thin ones. The potential changes in nerves, which are of the order of only a few microvolts, were amplified 100,000 times by means of a newly constructed amplifier and were recorded on a cathode-ray oscillograph, which provided a virtually inertialess recording device. Using this highly sensitive apparatus, Erlanger and Gasser found that nerve trunks contain fibers which conduct electrical impulses at different rates. They defined three groups of fibers: A fibers, those of greatest thickness, which conduct impulses at velocities between 5 and 100 meters per second (mps); B fibers of intermediate thickness, conducting at 3-14 mps; and thin, C fibers, whose conduction velocity is less than 2 mps.
In 1922 Erlanger and Gasser's preliminary observations were published, and the definitive work, "The Compound Nature of the Action Potential of Nerve as Disclosed by the Cathode-Ray Oscillograph," appeared in the American Journal of Physiology in 1924. An augmented version, published in book form in 1937, entitled Electrical Signs of Nervous Activity, has become a physiological classic. For their work they were awarded the Nobel Prize in physiology in 1944.
Erlanger's later work, which continued after his retirement and after his appointment as emeritus professor, was concerned mainly with the properties of single nerve fibers and, to a lesser extent, with synaptic function.
Erlanger was a man of retiring and introspective personality. His only hobby, he said, was "communion with nature." He combined a reflective mind with great manual dexterity, which made him a gifted experimentalist. He died in St. Louis on Dec. 5, 1965.
Further Reading
There is no detailed biography of Erlanger, but a short account of his life appears in Nobel Lectures: Physiology or Medicine, vol. 3 (1967) and in Lloyd G. Stevenson, Nobel Prize Winners in Medicine and Physiology, 1901-1950 (1953). The best account of his work is Joseph Erlanger and Herbert S. Gasser, Electrical Signs of Nervous Activity (1937). See also Charles Singer and E. Ashworth Underwood, A Short History of Medicine (1928; 3d ed. 1962). □
Erlanger, Joseph
ERLANGER, JOSEPH
ERLANGER, JOSEPH (1874–1965), U.S. physiologist and Nobel Prize winner. Erlanger, who was born in San Francisco, graduated from Johns Hopkins University in 1899. From 1906 to 1910 he was professor of physiology at Wisconsin Medical School and from 1910 held the chair of physiology at Washington University School of Medicine in St. Louis. He and Herbert Spencer Gasser received the 1944 Nobel Prize for physiology and medicine, for their work on the functional differentiation of nerves and on the influence of pulse pressure on kidney secretion. Erlanger made fundamental contributions to the knowledge of the cardiovascular and nervous system and to methods of physiological investigation. He invented a graphic method for measuring blood pressure and studied the mechanism of production of sounds used in measuring blood pressure by the auscultatory method. He studied nerve action potentials by cathode ray oscillograph; induction shocks as stimuli; traumatic shock and impulse initiation and conduction in the heart.
bibliography:
S.R. Kagan, Jewish Medicine (1952).
[Suessmann Muntner]