HöBER, RUDOLF OTTO ANSELM

(b. Stettin, Prussia [now Poland], 27 December 1873; d. Philadelphia, Pennsylvania, 5 September 1953)

physilogy.

Höber born into a family of shopkeepers and merchants. His mother, Elise Köhlau, was descended from one of the oldest merchant families in the city. After graduating from the Königlich Mariensstiftsgymnasium in Stettin, Höber enrolled in 1892 at the University of Freiburg im Breisgau, where he attended August Weismann’s lectures on zoology and studied chemistry with Baumann. His father’s financial difficulties soon forced Höber to leave Freiburg and continue his medical education at the University of Erlangen, where his uncle, the noted physiologist Julius Rosenthal, offered him financial assistance and a room in his home. Höber received his medical degree in 1897. In the following year he accepted a position as assistant at the Physiological Institute in Zurich.

In Zurich, Höber met Josephine Marx, Rosenthal’s niece. After their marriage in 1901, she studied medicine and became an accomplished physiologist. In the years prior to her death in 1941, she wrote several papers with her husband. Höber remained in Zurich until 1909, when he moved to the University of Kiel as a Privatdozent. In 1915 he was promoted to professor of physiology and director of the Institute for Physiology at Kiel. In addition to his teaching and extensive research and publication activities, Höber was coeditor with Albrecht Bethe of Pflügers Archiv für die gesammte Physiologie des Menschen und der Tiere from 1918 to 1933. In the latter years, as a result of the anti-Jewish laws. Höber was forced to surrender his position at Kiel and emigrate from Germany. He settled at the University of Pennsylvania, where he was visiting professor in the department of physiology from 1936 until his death.

Rosenthal’s suggestion that he make a detailed study of Walther Nernst’s textbook of physical chemistry led Hober to his major scientific achievements. Before completing his studies in Erlangen, he had decided to investigate general physiological processes from the standpoint of physical chemistry. By 1902 the first fruits of his program were recorded in his textbook Physikalische Chemie der Zelle und Gewebe, a work that went through six German editions and long remained the standard work on cellular physiology. An English edition of the book was published in 1945.

Hober’s scientific research was devoted almost exclusively to investigating physiological transport mechanisms, particularly through elucidating the properties, organization, and functional characteristics of cellular membranes, especially their permeability. The concepts of osmotic pressures, concentration gradients, and ionic and potential gradients derived from physical chemistry provided the basis for this enterprise, but Hober also coupled them with work on colloidal chemistry, a rapidly developing research area at the turn of the twentieth century. Work on the lipoid solubility of various staining agents, as well as microscopic investigation of their differential concentration in tissues and cell components. Were part of his investigation of the structure and permeability of cell membranes.

These research tools enabled Hober to propose a modification of Charles Overton’s lipoid model for cellular membranes. In order to explain how dissolved substances in the extracellular medium enter the protoplasm, Overton had proposed in 1895 that lipoids are the chief architectural components of cellular membranes and that the rate of penetration of organic compounds is determined by their solubility in the lipoids present in the membranes. Confirmation of this model was provided by experiments on the solubility of certain dyestuffs in a variety of solventlike membranes constructed from different organic fluids in the laboratory, such as solutions of olive oil, oleic acid, and diamylamine, or of cholesterol or lecithin with benzene or oil of turpentine.

Although the solubilities of the dyestuffs tested were comparable with their ability to penetrate and stain organic cells intravitally, Hober showed that the process was more complicated through experiments that revealed a variety of lipoid-insoluble substances that, at variance with the Overton solventmembrane concept, were nonetheless capable of entering cells at remarkable speeds. He demonstrated that these lipoid-insoluble substances have a low molecular volume and interpreted this as evidence in support of a porous, sievelike architecture of the cell membrane. Substances of high lipoid solubility that easily entered the cell turned out to have high molecular volume. From such experiments Hober proposed a mosaic as the general architecture of cell membranes consisting of at least two kinds of structural elements existing side by side at the surface of the cells: lipoid areas, which can vary in their chemical and physicochemical properties, and porous areas, which can vary in size and shape of the pores. Each occupies a different percentage of the total surface area.

Hober successfully utilized the’ lipoid-sieve’ model of the membrane in a wide variety of experimental researches elucidating the physiology of glandular secretion. His work on kidney function established the activity of tubular secretion and reabsorption in the lumen and tubular epithelium of the nephron, thereby adding support to the ultrafiltration theory of the formation of the glomerular filtrate first proposed by Carl Ludwig. The lipoidsieve concept also proved fruitful in Hober’s many investigations on the secretory activity of the liver.

Perhaps the most important area in which Hober applied his generalized concept of the membrane was investigations on the generation of bioelectric potentials. Early in his career he contributed significantly to elaborating models of muscle and nerve cell membranes essential to establishing julius Bernstein’s theory of the action potential. Bernstein conceived the action potential wave as a self-propagating depolarization resulting from the local breakdown of selectively permeable membranes surrounding nerve and muscle cells. The mechanisms controlling the transitory local alterations of the cell membranes were assumed to be chemical in nature.

In order to elaborate these mechanisms, Hober studied the effect of local application of neutral inorganic salts on the resting potential of the muscle. This work was later supplemented with experiments on synthetically produced colloid sieve membranes with varying pore sizes. Interfacial changes of ion concentrations in relation to pore size were studied by applying different electrolytes on each side of these artificial membranes. Comparing the results of studies on model membranes with experiments on physiological membranes. Hober hypothesized that as a result of polar changes in the concentration and composition of hydrogen, potassium, calcium ions, the hydroxyl ion, and aromatic sulfonates, the membranes undergo alterations of their colloidal structure that produce condensing or swelling effects combined with changes of resistance due to increased or decreased ion permeability. Following this chemical wave with concomitant loosening of the membrane, potassium ions concentrated in the cell interior would be permitted to diffuse across the membrane, leading to a depolarization of the nerve or muscle.

Höber’s willingness to adapt his concepts to new findings is illustrated by doubts he began to harbor toward the end of his career concerning his generalized model of cellular membranes. His lipoid sieve model employed passive transport mechanisms derived from physical chemistry. In his very earliest experimental researches on absorption in the intestines (1898, 1899), however, Höber pointed out that some substances moved against their concentration gradients and that some active transport system might be playing a role, but he did not explore this observation further at the time. He began to consider active transport mechanisms more seriously after experiments done in 1937 established that the absorption of amino acids through the walls of the intestine is in no way proportional to their concentration. Finally, in his publications after the mid 1940’s, Höber began to feel that the passive electrostatic mechanisms he had proposed for producing changes in membrane permeability were inadequate; and a decade before Hodgkin and Keynes’s revolutionary work on the sodium pump in 1955, he began to stress the need for exploring active, energyconsuming mechanisms for transporting ions in and out of cells that, he speculated, might be fueled by a cycle of phosphorylation and dephosphorylation.

BIBLIOGRAPHY

1. Original Works. Höber’s Habilitationsschrift is Über Konzentrationsänderungen bei der Diffusion zweier gelösten Stoffen gegeneinander (Zurich, 1899); his inaugural lecture at Zurich is’ Über die Bedeutung der Theorie der Lösungen für Physiologie und Medizin, ’ in Biologisches Zentralblatt, 19 (1899), 271-285, His books include Physikalische Chemie der Gewebe (Leipzig, 1902; 6th ed., 1926), also in English as Physical Chemistry of Cells and Tissues (Philadelphia, 1945), with the collaboration of David I. Hitchcock, J. B. Bateman, David R. Goddard, and Wallace O. Finn; and a general textbook, Lehrbuch der Physiologie des Menschen (Berlin, 1919; 8th ed., 1939).

In addition to his many research articles, the following offer a general overview of Höber’s developing views on the architecture of cellular membranes:’ Membranen als Modelle physiologischer Objekte, ’ in Die Naturwissenschaften, 24 (1936), 196-202;’ Membrane Permeability to Solutes in Its Relation to Cellular Physiology, ’ in Physiological Review, 16 (1936), 52-102;’ The Influence of Organic Electrolytes and Non-electrolytes upon the Membrane Potentials of Muscle and Nerve, ’ in Journal of Cellular and Comparative Physiology, 13 (1939), 195-218, written with Marie Andersh. Josephine Höber, and Bernard Nebel; and’ The Membrane Theory, ’ in Annals of the New York Academy of Sciences, 47 (1946), 381-392.

Among Höber’s works on secretory functions of the kidney and the liver are’ Studies Concerning the Nature of the Secretory Activity of the Isolated Ringer-Perfused Frog Liver, I, Differential Secretion of Pairs of Dyestuffs, ’ in Journal of General Physiological, 23 (1939), 185-190;’ Studies Concerning the Nature of the Secretory Activity of the Isolated Ringer-Perfused Frog Liver, 2, Inhibitory and the Promoting Influence of Organic Electrolytes and Non-electrolytes upon the Secretion of Dyestuffs, ’ ibid., 191-202, written with Elinor Moore; and’ Conditions Determining the Selective Secretion of Dyestuffs by the Isolated Frog Kidney.’ in Journal of Cellular and Comparative Physiology, 15 (1940), 35-46, written with Priscilla M. Briscoe-Woolley.

II. Secondary Literature. Biographical material on Höber is in Albrecht Bethe, ’ Rudolph Höber, ’ in Pflügers Archiv, 259 (1954), 1-3. An article on his work is H. Netter, ’ Rudolph Höbers wissenschaftliches Werk, ’ ibid., 4-13. See also J. C. Poggendorff, Biographisch-literarisches Handwörterbuch der exacten Naturwissenschaften, VIIa, pt. 2 (Berlin, 1958), 505.

Timothy Lenoir