Heidenhain, Rudolf Peter Heinrich

(b. Marienwerder, East Prussia [now Kwidzyn, Poland], 29 January 1834; d. Breslau, Germany [now Wrocław, Poland], 13 October 1897)

physiology, histology.

Among the physiologists of the second half of the nineteenth century Heidenhain has a special position as an independent worker and thinker not influenced by, and often opposed to, the modish currents of the time, especially to the tendency of oversimplification in the explanation of vital phenonomena and to the effort to reduce them to fairly simple physical and chemical processes. He was oriented more toward biological conceptions of vital phenomena than to their mathematical and physical interpretations. He did not trust preconceived opinions or theories, relying instead on the results of his experiments and on the inductive method.

Heidenhain was the eldest of twenty-two children of a physician. He very early revealed his talent and perseverance in work; his diligence in collecting plants and animals indicated his interest in the study of nature. After he completed his secondary education in his native town at the age of sixteen, he began the study of nature on an estate near his home but soon turned to medicine at the University of Königsberg; in this he was guided by his father, who had great influence on his early work and decisions. It was fairly common in Germany to attend several universities for undergraduate study, so Heidenhain went after two years to Halle, where A. W. Volkmann, one of the leading German physiologists of the time, turned his interest to physiology. After another two years he went to Berlin, where he finished his medical studies at the astonishingly early age of twenty years with a dissertation entitled De nervis organisque centralibus cordis, cordiumque lymphaticarum ranae (1854), which had been inspired by Emil du Bois-Reymond. In his dissertation Heidenhain refuted the opinion advanced by Moritz Schiff that the vagus nerve initiates the rhythmic contractions of the heart, demonstrating in his experiments that its function is to regulate heart activity; the automatic activity seemed to him to originate in the ganglia of the heart. Heidenhain remained with du Bois-Reymond at Berlin, working on the problem of the tonus of skeletal muscles and some other questions of nerve and muscle physiology. The results were published in his Physiologische Studien (Berlin, 1856).

In 1856 Heidenhain returned to Volkmann’s laboratory in Halle. The following year he submitted a Habilitationsschrift on the determination of the blood volume in the bodies of animals and men, improving on Hermann Welcker’s method. He married Volkmann’s daughter Fanny in January 1859, shortly before he assumed the chair of physiology at Breslau. Students at first revolted against the “unknown and green young professor,” and some older professors also showed their resentment: “One cannot have much respect for the discipline which can be represented by a twenty-five year-old teacher and master.” Nevertheless, through his diligence and competence, Heidenhain soon won respect and became one of the most illustrious members of the Breslau Medical Faculty, where he broadened his research activity and maintained it almost until his death in 1897.

In Breslau, Heidenhain continued his work on muscle and nerve, still under the influence of du Bois-Reymond. His most important accomplishment was the measurement of heat production during muscle activity. Although production of heat during a longer tetanic contraction had been found since 1805 by several observers, Heidenhain was the first to detect, by direct sensitive thermoelectric measurements, a minute increase in temperature (0.001–0.005°C.) during every simple twitch. He then studied the production of muscle heat under different conditions: for instance, the influence of the intensity of stimulation and of fatigue, and the relation of the heat produced to the work performed by a muscle lifting different loads. His most important finding was that the total energy output (heat and mechanical work) increases with increasing load (increasing active tension), an unexpected result. It showed that muscle liberated more energy when the resistance to its contraction was greater—that there is a kind of selfregulation of the energy expenditure in the working muscle—and thus that the muscle’s work is very economical. When fatigue sets in, the work becomes even more economical. Thermoelectric measurement has since become an important and widely used research tool in muscle physiology, for which Heidenhain’s classic work helped to form a basis.

Among Heidenhain’s other important findings in muscle and nerve physiology were that of increased acid formation in the working muscle and that of special motor reactions produced by stimulation of a sensory nerve after severance and degeneration of the motor nerve (1883), the so-called pseudomotor phenomenon, which was not explained until much later.

Heidenhain used the thermoelectric method in many other investigations, but it was not sensitive enough to detect heat production in nerve or in the brain during activity induced by stimulation of a sensory nerve. The latter gave a paradoxical result found to be a consequence of vascular reactions; this led Heidenhain to further investigations of vasomotor reactions, a topic to which he and his pupils repeatedly turned. He contributed greatly to the knowledge of vascular reactions in the skin, muscles, and glands and to the problem of cardiovascular regulation in the early period of their study.

In 1867 Heidenhain began systematic studies of the physiology of glands and of the secretory and absorption processes, which remained his chief field of interest for the rest of his life. His great advantage in these studies was his knowledge and practical experience in histology. Thus he noticed morphological changes in salivary glands during their secretory activity (1866) and differentiated the serous glands from the mucous ones. He showed that secretion of saliva is largely independent of the blood flow and studied the effects of stimulation of nerves, distinguishing the “trophic” nerve fibers activating the metabolism of glandular cells from secretory fibers bringing about a passage of fluid from capillaries through the cells, washing the specific products out of the cells and into the secretory ducts. He described the difference between stimulation of parasympathetic and sympathetic nerves, the latter causing only a small secretion of a concentrated fluid. He concluded that secretion is an intracellular physiological process rather than a mechanical one.

Heidenhain noticed in the stomach two types of cells in the gastric glands and showed that one secretes the enzyme pepsin, the other hydrochloric acid. He worked out a method of a “small stomach” or gastric pouch, later improved by I. P. Pavlov, who worked for some time in Heidenhain’s laboratory and always held Heidenhain in great esteem. The gastricpouch technique has been widely used in several modified forms and has proved extremely useful in the investigation of gastric secretion and its regulation. Heidenhain also studied secretion in the pancreas, the liver, and the intestinal glands. Equally important were his studies of absorption processes in the intestine, which showed that absorption takes place from the interior of an isolated loop, even against a concentration gradient. Thus he came to the conclusion that intestinal absorption cannot be a simple physicochemical process but, rather, is a physiological activity performed by the epithelial cells.

Studies of the secretory activity of glands led Heidenhain to extensive investigations of the process of urine formation in the kidney. In 1842 William Bowman, through his study of the microscopic structure of kidney, developed a hypothesis that the renal tubules have a function in the secretion of specific constituents of urine (urea, uric acid, and so on) and that the Malpighian corpuscle might be an apparatus destined to separate the watery portion of the urine from the blood. Soon afterward Carl Ludwig, one of the four main exponents of a mechanistic physiology aimed at describing all vital phenomena in terms of simple physical and chemical processes, pointed out that the glomerulus, a tuft of capillaries projecting into the wide beginning of a long suite of renal tubules (Bowman’s capsule), is a device by which a filtrate (or, rather, an ultrafiltrate without large protein molecules) may be separated from the blood plasma, and that in its further passage urine is formed by diffusion of a large proportion of water back into the capillaries surrounding the tubular system.

There had been several serious objections to Ludwig’s filtration-diffusion theory; and Heidenhain, an experienced histologist, was convinced that the very complicated structure of the renal tubules, similar to that of other glands, pointed to a similarity in function. He found in his own experiments and those of others many indications that tubular cells play an active role in the formation of urine, as well as other objections to Ludwig’s theory. Eventually he formulated his own theory, a modification of Bowman’s. The urine was formed, he believed, by the secretory activity of tubular cells transporting (against a concentration gradient) urea, uric acid, and other specific constitutents of urine from the blood; in the tubules the constituents would be washed off by the flow of glomerular fluid. In his criticism of the filtration theory Heidenhain for a long time appeared to be right on several points, such as the role of renal tubules in performing physical work by actively transporting substances against concentration gradients. But he was clearly mistaken in rejecting two important points: the idea of glomerular filtration (ultrafiltration) and the concentration of the specific urine constituents during the passage of filtrate through the tubular system. In the latter process both physical processes (diffusion and concentration in the countercurrent system of Henle’s loop) and metabolic processes (active transport) may play roles. But this transport (active resorption) is mainly in a direction opposite to that assumed by Heidenhain.

In recent reviews of research and concepts in kidney physiology the subject has been often presented as if the truth had always been on the side of Heidenhain’s opponents. Urine formation in the kidney is an extremely complicated process, and it required almost eighty years after Heidenhain to trace its main features. Many hypotheses were formulated, each of them containing both correct and erroneous points. Heidenhain’s chief merit was that his sober criticism, based on reliable experiments, stimulated discussion and further research at a time when renal physiology had been stagnant for about thirty years. His research contributed to the progress of knowledge more than if he had accepted a hypothesis which still required many corrections and substantial amendments.

Finally, Heidenhain’s experiments on hypnotism (animal magnetism), made in an attempt to study the phenomenon scientifically, and his treatise defending the necessity and utility of vivisection in medical research should be mentioned.

Heidenhain’s reliance on experiment as a sure guide in the search for truth, his technical skill, his wide-ranging work, his assiduity, and his independent thinking greatly influenced his contemporaries, especially those who had passed through his laboratory, such as Pavlov, Starling, and W. B. Cannon.

BIBLIOGRAPHY

I. Original Works. Heidenhain’s publications include Mechanik, Leistung, Wärmeentwicklung und Stoffumsatz bei der Muskeltätigkeit (Leipzig, 1864); Physiologie der Absonderungsvorgänge (Leipzig, 1880), also in L. Hermann, ed., Handbuch der Physiologie, V, pt. 1 (Leipzig, 1883), 1–420; Der sogenannte thierische Magnetismus. Physiologische Beobachtungen (Leipzig, 1879; 4th ed., 1880), trans. from the 4th German ed. by L. C. Woolbridge as Animal Magnetism. Physiological Observations (London, 1880); and Die Vivisektion im Dienste der Heilkunde (Leipzig. 1879).

Heidenhain’s papers were published first in the collection Physiologische Studien (Berlin, 1856), then in the series Studien des Breslauer Physiologischen Institutes, 4 pts. (Leipzig, 1861–1868), and the rest mostly in Pflüger’s Archiv für die gesamte Physiologie des Menschen und der Tiere. A partial bibliography was collected by P. Grützner, in Pflügers Archiv, 72 (1898), 263–265; papers published in Pflügers Archiv are listed in its Registerband for 1–30 (1885), pp. 24–26, and for 31–70 (1900), p. 20.

II. Secondary Literature. See J. Bernstein, “Rudolph Heidenhain,” in Naturwissenschaftliche Rundschau, 12 (1897), 606–607, and P. Grüzner, “Zum Andenken an Rudolf Heidenhain,” in Pflügers Archiv, 72 (1898), 221–265; and in Allgemeine deutsche Biographie, L (1905), 122–127. See also P. W. Herron, “Rudolf Heidenhain of Breslau,” in Surgery, Gynecology, and Obstetrics, 110 (1960), 223–225.

Vladislav Kruta