BOHR, CHRISTIAN HARALD LAURITZ PETER EMIL

(b. Copenhagen, Denmark, 14 February 1855; d. Copenhagen, 3 February 1911)

respiratory physiology.

Bohr was the son of Henrik G. C. Bohr, the headmaster of a school, and of Augusta L. C. Rimestad. He entered Copenhagen University in 1872, became assistant to Peter L. Panum in 1878, and received the M.D. degree in 1880. He married Ellen Adler, daughter of a prominent Jewish financier, in 1881 in a civil ceremony. Their sons were Niels and Harald. After postdoctoral work with Carl Ludwig at Leipzig, Bohr settled in Copenhagen in 1883 and succeeded Panum as professor of physiology in 1886.

Bohr’s first publication (1876) concerned the effect of salicylic acid on digestion of meat in dogs, his M.D. dissertation (1880) dealt with fat globules in milk, and his first publications from Ludwig’s laboratory (1881, 1882) related the strength of muscle contraction to the frequency and strength of stimulation. His subsequent research stemmed from Ludwig’s interest in respiration. Under Ludwig, Bohr devised an absorptiometer and began a lifelong studs of the absorption and dissociation of respirators gases in various media, including hemoglobin solutions, whole blood, and intact animals. His 1885 paper on deviations of oxygen from the Boyle-Mar iotte law indicates his meticulous physical approach, Characteristically he strove for accurate quantitation under physiological conditions. He trusted his observations rather than generally accepted theory. This policy led him to some erroneous conclusions when methods were not as accurate as he thought. but even his mistaken ideas sometimes led to contributions of lasting importance.

To measure the pressures of oxygen and carbon dioxide in arterial blood in vivo. Bohr devised a tonometer that formed an arteriovenous shunt in experimental animals (1891). To compare these pressures with those in alveolar gas, he crystallized previously hazy notions of respirators dead space into an equation for calculating alveolar gas composition from the compositions of inspired and mixed expired gas, the total volume of the breath, and the anatomical dead space volume, which he measured by filling the tracheobronchial tubes with water at autopsy. This “Bohr equation” remains fundamental to gas-exchange theory and is still used the reverse) to calculate the dead space volume of patients from their alveolar gas composition, which cm now be estimated independently. The data Bohr obtained in these experiments, however, indicated that arterial blood sometimes had an oxygen pressure higher (and carbon dioxide pressure lower) than simultaneous alveolar gas (1891). This led him to accept the theory that the lungs could act like a gland to secrete gases against a pressure difference when necessary. John Scott Haldane of Oxford provided strong support, but many others disagreed. Throughout his life Bohr and his students sought better evidence.

Their studs of blood reached its peak when Bohr and two students, Kail A. Hasselbalch and August Krogh, using a precise microtonometere that Krogh devised, first measured in vitro the entire equilibrium curve of oxygen and whole blood (1904). They found that the curve was sigmoid, not hyperbolic (as the generally accepted theory required). Bohr continued to suppose that hemoglobin existed in multiple forms with different affinities for oxygen; in retrospect the finding opened the door to the modern concept of four interacting binding sites within a single molecule.

The same experiments also revealed that the affinity of hemoglobin for oxygen was inversely affected by carbon dioxide pressure. Their 1904 paper pointed out that this “Bohr effect” greatly facilitates oxygen uptake in pulmonary capillaries, where carbon dioxide is lost, and release of oxygen in peripheral capillaries, where carbon dioxide is gained. Bohr was unable to demonstrate the converse effect of oxygenation on carbon dioxide binding; that effect was established by an Oxford team that included a former student, Johanne Christiansen (1914).

Bohr’s last important contributions to gas transport resulted from an attempt to distinguish the rate of supposed oxygen secretion from the simultaneous physical diffusion of oxygen down its pressure gradient (1909). Although the oxygen pressure in alveolar gas could he calculated by the Bohr equation, the oxygen pressure on the other side of the alveolar membrane could not be measured directly because it changed continuously and alinearly along the capillaries as oxygen entered the moving blood and reacted with hemoglobin. From his empirical oxygenhemoglobin equilibrium curve of 1904, Bohr devised a graphical integration to calculate the mean oxygen pressure in the pulmonary capillaries. “Bohr integration” is still used to estimate the change in blood oxygen concentration along the pulmonary capillaries.

In this 1909 paper Bohr also described a method to determine the capacity of lungs in vivo for physical diffusion of oxygen despite the supposed presence of simultaneous oxygen secretion. Carbon monoxide is not secreted, and its diffusing capacity can be measured directly because that gas binds so tightly to hemoglobin that its pressure in pulmonary capillary blood remains negligible. The diffusing capacity for oxygen can then be calculated from the solubilities and molecular weights of the two gases, Bohr concluded that the diffusing capacity. which he calculated from measurements made at rest, was inadequate to account for oxygen uptake in heavy exercise: secretion seemed necessary.

August and Marie Krogh, while also looking for better evidence for the secretion theory, had already found in 1906 that the diffusing capacity for carbon monoxide increased in exercise enough to make oxygen secretion unnecessary, but they kept this observation secret. They hesitated to contradict their teacher without more evidence. They quietly continued looking until 1910, when their accumulated evidence against secretion became too convincing to be kept concealed. The carbon monoxide principle outlasted the secretion theory and is now used routinely to evaluate diffusion in pulmonary disease.

Initiating a new line of research, Bohr published in 1906 his first report on total lung volumes measured by hydrogen dilution and, in 1910, a significant study of pathological lung enlargement in pulmonary emphysema. The latter was his last research publication before his sudden death.

Despite his errors Bohr was the major contributor of his day to present understanding of respiratory gas transport. He made another lasting contribution as a teacher. Like Ludwig, he worked closely with his students in the laboratory, inspiring them to pursue lofty goals. He founded the Danish school of respiratory physiologists, which has continued to flourish.

BIBLIOGRAPHY

I. Original Works. Obituaries that list and summarize Bohr’s publications include Carl J. Salomonsen. Festkrift udgivet af Københavns Universitet i anledning af universitetets årsfest Nov. 1911 (Festschrift published by Copenhagen University for the university’s anniversary… : Copenhagen, 1911), 53–58, which cites original Danish publications and earlier obituaries; and Robert Tigerstedt, “Christian Bohr: Ein Nachruf,” in Skandinavisches Archiv für Physiologie, 25 (1911), ix-xviii, which cites the German versions. For English translations of his papers on Bohr’s equations, Bohr’s effect, and Bohr’s integration, see John B. West, ed., Translations in Respiratory Physiology, I. S. Levij. trans. (Stroudsburg, Penu., 1975). Archival material preserved in the Institute of Medical Physiology of the University of Copenhagen includes his extensive correspondence with Ludwig.

II. Secondary Literature. Genealogies and biographies of Bohr and many of his relatives and associates are included in S. C. Bech. ed., Dansk biografisk leksikon (Danish biographical dictionary), 3rd ed. (Copenhagen, 1979–1984). N. Zuntz expressed the view of a scientific opponent in Medizinische Klinik (Berlin). 7 (1911), 434, L. S. Fridericia published a tribute in V. Meisen. ed., Prominent Danish Scientists (Copenhagen and Oxford, 1932). Recent evaluations of his work in historical perspective include John T. Pdsall, “Blood and Hemoglobin…,” in Journal of the History of Biology, 5 (1972), 205–257; and P. Astrup and J. W. Severinghaus. The History of Blood Gases. Acids and Bases (Copenhagen, 1986), Bodil Schmidt-Nielsen summarized his influence on Krogh in “August and Marie Krogh ami Respirators Physiology,” in Journal of Applied Physiology, 57 (1984), 293–303. His personal life and character are lecalled in Stefan Rozental, ed., Niels Bohr (New York, 1967).

Ralph Kellogg