(b. Newry, Ireland, 23 July 1872; d. Cambridge, England, 21 March 1947)
Barcroft was descended from a branch of a landed English family who had become Quakers and had moved to Ireland during the seventeenth century. His father, Henry Barcroft, was active in the management of a spinning company and a tramway company, and contributed mechanical inventions important to the operations of each. He was also an artist and was interested in natural history.
Joseph Barcroft grew up a Quaker and remained active within the Society of Friends until he came to disagree with its views during World War I. Sent to the Leys School at Cambridge in 1888 because of his interest in science, Barcroft took a B.Sc. at the University of London by passing the examinations while still a student at Leys. After a year off in 1892–1893 because of overstrain, he entered King’s College, Cambridge, to study natural science. After his graduation in 1896 he began original research in the Cambridge Physiological Laboratory, founded and directed by Michael Foster. In 1899 he was elected to a fellowship at King’s College, and in 1905 also became a lecturer of the college. He held these positions for nearly fifty years. In 1925, upon the death of John Newport Langley, Barcroft became professor of physiology. He married Mary Agnetta Ball in 1902.
Barcroft’s first investigation was suggested to him in 1897 by Langley, who was then Foster’s assistant. For many years Langley had been investigating the process of glandular secretion. Rudolf Heidenhahn had theorized that there are two types of nerves supplying the salivary glands, but Langley became convinced that there was no evidence for more than one kind of secretory nerve fiber, and that the differences in the character of salivary secretions obtained when the chorda tympani and the cervical sympathetic nerves leading to the gland are stimulated could be explained by vasomotor effects. Langley encouraged Barcroft to try to measure the effects of stimulating the submaxillary gland upon its metabolism, in order to throw light on the issue of its innervation.
When Barcroft took up the topic, however, the accurate measurement of the changes in the amounts of gases exchanged in the organ became in itself an absorbing problem, one on which he worked for several years. He had first to refine the methods for extracting blood gases so that he could analyze samples of blood much smaller than were customarily used. In 1901 he and John Scott Haldane developed a method by which he could measure quickly and accurately the gases contained in 1 cubic centimeter of blood. The physiological problem of estimating the gaseous exchange of the gland was, he saw, more complex than previously realized. It was not enough merely to measure the quantities of gases in equal volumes of arterial and venous blood and the amount of blood flowing out of the gland in a given time in order to calculate the rate of exchange, for he found that the hemoglobin in the venous blood was more concentrated because some of the water of the blood had been lost as salivary fluid. After he had taken such changes into account in his calculations, he was able to show that stimulation of the chorda tympani substantially increased the oxygen uptake and carbonic acid output.
In the following year Barcroft turned the methods he had developed for this research to the study of other organs. In 1904, in collaboration with Ernest Starling, he showed that the pancreas also consumes more oxygen and releases more carbonic acid when it is secreting than when it is not. Next he turned to the kidney and to the heart, finding in each case a correlation between increased or decreased activity and the rate of metabolism of the organ.
In his early blood gas analyses Barcroft dealt only with the amounts of these substances in the arterial and venous blood samples. Other physiologists, however, including especially Christian Bohr, had been investigating the relation between the percentage saturation of the blood with oxygen and the tension of the oxygen in the blood, the latter being proportional to the pressure of oxygen in the atmosphere with which the blood sample was in equilibrium. They were attempting to construct characteristic curves with which they could calculate either quantity when the other was known. Bohr emphasized that it was the oxygen tension in the plasma of the venous blood, rather than the percentage saturation of the hemoglobin with oxygen, which most directly determined the amount of oxygen that reaches the cells. Accordingly, he calculated from Barcroft’s figures for the quantities of oxygen in the venous blood of the submaxillary gland the corresponding oxygen tension, and showed that it increased by 48 percent after the gland was stimulated.
Undoubtedly impressed by the application Bohr had made of his “own figures,” Barcroft returned in 1905 to the submaxillary gland, to take up the problem inherent in Bohr’s approach: how oxygen is transferred from the blood to the secretory cells. Barcroft noticed, however, a striking anomaly: the available analysis of saliva showed that it contained a larger percentage of oxygen than the blood plasma did, according to Bohr’s calculations. It was hard to imagine how this concentration could occur. Barcroft thought that there was no recourse but to assume that there was active cellular secretion of oxygen in the capillary walls, unless the oxygen dissociation curves were incorrect, so that they gave a calculated oxygen tension that was too low. The problems thus raised in response to Bohr’s discussion became prominent themes in Barcroft’s work during the following years.
Examining more closely the previous literature on oxygen dissociation curves, Barcroft realized that the results were widely discordant. He decided, therefore, to check the curves for himself. At first he and his research associate, Mario Camis, seemed to obtain a uniformity of results that had eluded their predecessors. Blood of different kinds of animals, which before had given divergent results, came out the same for them. But when they used human blood, they could not obtain a similar agreement. Only after “six months of research which became weekly more depressing,” as Barcroft recalled, did they finally discover that a variation in the salts present in a solution of hemoglobin alters the hemoglobin’s dissociation curve for oxygen. Systematically examining the effects of other changes in the salts, they found that they could reproduce curves consistently whenever they kept the composition of the solution constant.
Following this success, Barcroft’s main focus of research shifted to further elucidation of the oxygen dissociation curve. He pursued two distinct but interlocking lines of investigation. First, principallyin collaboration with A.V. Hill, he tried to characterize the curves mathematically and derive from the characteristics of the reaction between hemoglobin and oxygen a theory of the mechanism of their interaction. Second, he continued to study the conditions that modify the curve. A rise in temperature from 36° to 41° C., he discovered, shifted the curve so that at a given tension the blood was less saturated with oxygen. The addition of lactic acid to the blood modified the curve in the same direction. He saw both these effects as having adaptive significance to the animal, for they would aid in the discharge of oxygen in the tissues when the latter were in conditions of stress, which require more rapid delivery of oxygen.
In his first paper on the dissociation curve, Barcroft considered some implications of the curve’s properties for conditions at high altitudes. Shortly after, Nathan Zuntz of Berlin invited him to join an expedition to the island of Tenerife. The group, whose purpose was to examine the biochemical effects of high climates and solar radiation, operated from three stations on the island: at sea level, 7,000 feet, and 11,000 feet. Because Bohr had shown that a change in the carbonic acid concentration in the blood displaces the oxygen dissociation curve, Barcroft expected that at high altitude, where the alveolar CO2 pressure is reduced, the curve would be so modified. Contrary to his prediction, he found the results for blood samples taken at 11,000 feet to be the same as for those taken at sea level. If, on the other hand, he analyzed the blood sample taken at high altitude after putting it in equilibrium with carbonic acid at a pressure equivalent to the alveolar pressure at sea level, the curve was displaced. Consequently, the blood itself must have changed in such a way that its dissociation curve at the lower pressure duplicated that of normal blood at a higher pressure. He thought that probably some substance such as lactic acid was taken up in the blood in place of the decreased carbonic acid. “This change,” he concluded. “compensated the change in alveolar CO2 tension to such an extent that the actual dissociation curve under the conditions locally established did not alter.” He considered it probable that this was one of the mechanisms produced in the process of evolution that enabled “the respiratory process to adapt itself to various unusual conditions.”
After returning from Tenerife, Barcroft continued the two basic lines of research that he had established. He investigated the metabolism of the submaxillary gland, the kidneys, and the liver, becoming more deeply involved in the special problems each organ presented for measuring the gaseous exchange, the oxygen consumption, the work performed, and the relation between circulatory changes and activity. At the same time he delved further into the physical chemistry of hemoglobin. In 1910 A.V. Hill developed a mathematical equation from which he could derive the oxygen dissociation curve, and from which he could make deductions concerning such properties as the state of aggregation of the hemoglobin molecules. The equation also enabled Barcroft to treat more precisely and quantitatively the alterations of the dissociation curve with altitude and with other changes in conditions. In 1913 Barcroft summarized the results of his researches over the preceding sixteen years in The Respiratory Function of the Blood, generally regarded as a landmark in the development of respiratory physiology.
During World War I, Barcroft contributed to the national effort by investigating the effects of gas poisoning and methods for treating patients suffering from it. In 1915 he went to Boulogne to study gassed soldiers at the base hospital; in 1917 he was made a member of the Chemical Advisory Committee of the British government, and took charge of its physiological work in a laboratory established at Porton. His work was related to his prewar research, for he saw that the symptoms of gassed patients were often the result of inadequate respiration caused by damage to the lungs. “The fundamental idea on which our treatment is based,” he reported, “is that the whole train of symptoms shown by these patients is the same as that exhibited at high altitudes.” His wartime experiences also helped to broaden his view of the factors involved in respiration, by emphasizing to him the importance of the chemical buffers of the blood for controlling its alkalinity.
After the war Barcroft extended his study of highaltitude physiology. In 1922 he led an expedition to the Peruvian Andes to study the ways in which the human body adapts to an environment of low oxygen pressure by changes in the oxygen dissociation curve of its blood, increases in pulmonary ventilation and the concentration of hemoglobin in the blood, and other factors. He also continued to examine a question often debated among contemporary physiologists: whether the pulmonary epithelium secretes oxygen into the blood under such conditions. He concluded that his own evidence did not support the assertion that it does.
While making, incidental to this expedition, measurements of the total volume of human blood, Barcroft observed an anomaly that helped start him on a new line of research. To determine the volume, he had the subject inhale a known quantity of carbon monoxide and then measured its concentration in a few drops of the subject’s blood. The object was to compare the volume at higher altitude with that at sea level, but the volume at sea level turned out to be greater when the temperature was high than when it was low. This result raised the question of whether there was in the body a reservoir of blood and hemoglobin not detectable by the carbon monoxide method. Suspecting the spleen to be such a site, Barcroft established that in animals exposed to carbon monoxide, that gas penetrated the hemoglobin of the spleen significantly more slowly than it did the hemoglobin of the general circulation, suggesting that the spleen does retain a store of hemoglobin. Between 1925 and 1928 he developed several methods for observing changes in the size of the spleen, so that he could tell whether it adds a significant amount of blood to the circulation when it contracts. He found not only that it does, but that its contractions are correlated with increased demands for circulating blood, so that the organ serves as a regulator of blood volume.
In 1928 Barcroft found “in a somewhat accidental way” that the spleen of a pregnant dog was contracted, an observation which made him wonder what quantity of blood was needed in the uterus during pregnancy In 1932 he measured the amount and found it unusually large, even while the embryos were still very small. He then asked whether this quantity served for storing blood or whether an unusually large volume passed through the uterus. While measuring the blood flow and gaseous exchanges of the organ, he discovered that the percentage saturation with oxygen of the venous blood in the uterus gradually declined during pregnancy, until it reached such a low level that it was hard for him to imagine how any further oxygen could be transferred to the embryonic circulation. The gravity of the problem launched him on a full investigation of fetal respiration, which broadened into a study of embryonic circulatory and nervous development. He continued his research on fetal physiology until his death.
Although known chiefly as a resourceful experimentalist with a sure grasp of significant problems, Barcroft also took time to write more broadly on the nature of physiological processes. The most notable of these efforts was Features in the Architecture of Physiological Function (1934), in which he discussed general functional principles that he considered to be manifested repeatedly in specific mechanisms within animals. Among such principles were the fixity of the internal environment, the provision of stores of materials, “all-or-nothing responses,” and the view that “every adaptation is an integration,” Barcroft was regarded as an inspiring teacher and a warm, sensitive person, combining gaiety with seriousness, and disciplined, forceful leadership with generosity and informality.
I. Original Works. Barcroft’s books include The Respiratory Function of the Blood (Cambridge, 1914); The Respiratory Function of the Blood, pt. I, Lessons From High Altitudes (Cambridge, 1925); The Respiratory Function of the Blood, pt. II, Haemoglobin (Cambridge, 1928); Features in the Architecture of Physiological Function (Cambridge, 1934); The Brain and Its Environment (New Haven, 1937); and Researches on Pre-natal Life (Oxford, 1946). The majority of his research papers appeared in the Journal of Physiology. Full bibliographies are given in the two works below.
II. Secondary Literature. Works on Barcroft are Kenneth J. Franklin, Joseph Barcroft 1872–1947 (Oxford, 1953); and F. J. W. Roughton, “Joseph Barcroft 1872–1947,” in Obituary Notices of Fellows of the Royal Society, 6 (1949), 315–345.
Frederic L. Holmes