(b, Louisville, Kentucky, 23 April 1873; d. La Jolla,l California, 18 February 1944)
Henderson was the son of Isham and Sally Nielsen Yandell Henderson. His father was an engineer and the owner and founder of the Louisville Courier-Journal. Henderson received his B.A. from Yale in 1895 and then entered the Yale graduate school to study physiological chemistry under Russell H. Chittenden. He was a member of the naval militia from 1897 to 1899 and served as an ensign for one summer on the U.S.S. Yale during the Spanish-American War. In 1898 he received his Ph.D. and then undertook further studies in Germany for two years with Albrecht Kossel and Carl Voit. In 1900 Henderson returned to Yale as an instructor in physiology and spent the rest of his career there. He retired in 1938 but continued to work as professor emeritus until his death. Henderson’s work brought him numerous awards and honors, including election to the National Academy of Sciences and an honorary M.D. from the Connecticut State Medical Society.
A militant man who fought strongly for his beliefs, Henderson was an active member of the Progressive party and an unsuccessful candidate for Congress in 1912 and 1914. As a scientist he did not hesitate to improvise and use crude, homemade equipment to perform his experiments. In constructing various pieces of apparatus, Henderson sometimes utilized such common objects as a child’s rubber ball, the top of a tobacco tin, and a piece of garden hose. Like his friend J. S. Haldane, whom he greatly admired, he criticized attempts to explain physiological phenomena solely in terms of chemistry and physics. He was also like Haldane in his willingness to act as a subject in his own experiments.
His physiological researches were devoted almost exclusively to respiration and circulation. In 1903 Henderson began an investigation of the volume changes of the mammalian heart. This study led him to the ideas which essentially dominated his thought for the rest of his life. He became convinced that the venous return largely determines the volume of blood that the heart can pump. Failure of the circulation, he concluded, was due to failure of the mechanism controlling venous return, which he termed the “venopressor mechanism,” and not to failure of the cardiac or vasomotor mechanism.
In the course of this work it was necessary to make a wide incision in the thorax of the experimental animals (dogs) in order to place the cardiometer on the heart. Under these conditions the lungs were collapsed, and air had to be blown into them to maintain respiration. On one occasion the apparatus for artificial respiration was out of order, and air had to be supplied to the lungs by means of a hand bellows attached to the trachea and operated by a janitor. Henderson noticed that the blood pressure was falling even though the heart rate was high, and he supposed that respiration was insufficient. But when the artificial respiration was increased, the animals collapsed and died even more rapidly. If artificial respiration was administered less vigorously, but still in excess, the dog passed into shock. This observation eventually led Henderson to the conclusion that the decrease in carbon dioxide which accompanies excessive pulmonary ventilation is the cause of shock. The discovery by Haldane and his co-workers in 1906 that carbon dioxide plays a role in the control of respiration reinforced Henderson’s conviction of the importance of this substance in physiological processes.
Henderson’s greatest contribution to science was probably in the practical application of his ideas. He introduced the technique of administering a mixture of carbon dioxide and oxygen, instead of only oxygen, as a method of resuscitation. His conviction that carbon dioxide stimulated circulation and respiration led him to use carbon dioxide-oxygen inhalation as treatment for carbon monoxide poisoning, surgical shock, asphyxia of newborn babies, and similar conditions. This technique proved very successful and saved countless lives. Henderson also became involved in the design of mine rescue apparatus and in the fixing of ventilation standards for the Holland Tunnel. During World War I he supervised the production of gas masks for the Chemical Warfare Service of the U.S. Army.
The use of carbon dioxide in resuscitation was opposed by some on theoretical grounds: it was regarded by many as a poison which had to be eliminated from the body. In addition, patients in states of carbon monoxide asphyxia, shock, and similar conditions already had a low blood-alkali content and thus appeared to be in a condition of acidosis. It was feared that administration of carbon dioxide would aggravate this condition. Henderson showed that a decrease in the blood bicarbonate level does not always involve an excess production of acids and a lowering of the blood pH. In many cases, hyperventilation causes a severe drop in the carbon dioxide tension of the blood. The blood bicarbonate is then also reduced in an effort to keep the pH from rising, but total compensation may not be achieved. Thus it is possible to have a situation in which the blood bicarbonate level is lowered but the blood pH rises instead of falls, a condition now referred to as “respiratory alkalosis.” In such cases administration of carbon dioxide can be beneficial.
Henderson’s theories did have their shortcomings. For example, he exaggerated the role played by the venous return in regulating the circulation. In his desire to discredit the then current theory of acidosis, he placed too much emphasis on depressed or increased breathing as cause of low or high blood pH. Factors such as the increased production of acids and the failure of the kidneys to excrete sufficient amounts of acid are causes of acidosis—in the sense of low pH—more frequently than he believed.
In the 1930’s Henderson developed an elaborate theory concerning the effect of muscle tonus on physiological processes. He felt the normal reflex muscle tonus was an extremely important factor in maintaining the respiration and circulation. Carbon dioxide acted to increase muscle tonus, and this phenomenon explained in part its effectiveness in conditions such as shock. While tonus apparently does play a role in physiological processes such as circulation, Henderson overestimated its importance.
I. Original Works. A complete bibliography of Henderson’s works has not been published. A fairly extensive bibliography including all of his most important works appears in his Adventures in Respiration (Baltimore, 1938), pp. 288–295, a summary of his major contributions which contains a significant amount of autobiographical material. His most important scientific monograph, written in collaboration with Howard Haggard, is Noxious Gases and the Principles of Respiration Influencing Their Action (New York, 1927). His interest in America’s liquor problem is revealed in A New Deal in Liquor: A Plea for Dilution (Garden City, N.Y., 1934). Two important series of papers by Henderson and his co-workers are eight papers entitled “Acapnia and Shock,” in American Journal of Physiology (1908–1918), and twelve papers entitled “Hemato-respiratory Functions,” in Journal of Biological Chemistry (1919–1921).
Secondary Literature. The only biographies are short sketches, mostly in the form of obituary notices, including Howard Haggard, in Year Book. American Philosophical Society (1944), pp. 369–374; C. G. Douglas, in Nature, 153 (1944), 308–309; and Cecil Drinker, in Journal of Industrial Hygiene and Toxicology, 26 (1944), 179–180. An anonymous biographical article on Henderson also appears in National Cyclopedia of American Biography, XXXVI (New York, 1950), 25–26.”