August Krogh

Danish physiologist

• Born: November 15, 1874
• Birthplace: Grenaa, Denmark
• Died: September 13, 1949
• Place of death: Copenhagen, Denmark

Krogh, who had been aided by co-researcher Marie (Jorgensen) Krogh in his studies, won the 1920 Nobel Prize in Physiology or Medicine for his investigations into how the capillaries regulate the flow of blood, and thus oxygen, in the body. The married couple also made important advances in the understanding of how the lungs exchange oxygen from the air into the bloodstream.

Early Life

August Krogh (kroh) was born in the town of Grenaa in Jutland on November 15, 1874. His father, Viggo, had been a shipbuilder, but the time of the large wooden ships was past. By the time of August’s birth, he had bought a small brewery. In this business, he supported his wife, Mimi Drechman Krogh, and his six children, August being the eldest. Money was never in abundance for the Kroghs, and August learned early to be frugal; even later, when large funds were available to him in his research, he still used scraps of paper for his notes.

In his schooling, August exhibited an independent nature. He found formal schooling boring but pursued his interests in nature and physics outside school, watching the behavior of insects and spiders for hours. One teacher, Carl Nilsson, recognized the potential of the frustrated student and gave him the individual attention he needed. In a letter to his future wife, August recounted how he and Nilsson spent an afternoon together with a new telescope the boy had received for his confirmation. They took the instrument apart and studied how the lenses worked. They discovered that the ocular could be used as a small microscope, and soon August had made a wooden holder for it and began studying everything within reach.

Another strong influence that helped August in finding his profession was a friend of the family, William Sorensen. Sorensen, a zoologist, spent many summer vacations in Grenaa with his friend Viggo. August, in his youth, enjoyed walking with him, scouring the fields. On entering the University of Copenhagen in 1894, he took Sorensen’s advice and attended a class taught by Christian Bohr (father to physicistNiels Bohr), an eminent physiologist. After the first lecture, on quantitative methods for determining the blood volume of the human body, August decided that such studies appealed to him most. He became Bohr’s student but held his earlier interest, zoology, and was graduated in that subject in 1899.

Life’s Work

Krogh is best known for his work on capillaries, but respiration and the exchange of oxygen in the body was the unifying theme of his endeavors. For his doctoral research, under Bohr’s supervision, he investigated the respiration of the frog. He concluded that the animal took in oxygen through the lungs, but that the more diffusible carbon dioxide escaped through the moist skin.

In 1905, Krogh married Marie Jorgensen, a physician and researcher, and the two started the research that would cut Krogh’s ties to Bohr. Bohr believed that the lungs secreted oxygen into the bloodstream using cells controlled by the nervous system. For a time, Krogh followed this theory but agreed that conclusive evidence to support it was lacking. To answer the question of whether gas exchange in the lungs was passive or active, Krogh used his microtonometer, a small gas-analyzing apparatus he designed for work on insect respiration. The microtonometer could measure the air pressure of an air bubble of only about ten cubic millimeters, or about the size of a pinhead. With this instrument, Krogh could measure the oxygen tension of the blood and compare it to that of the lung alveolus. In 1909, in seven papers that the Kroghs later called “the seven small devils,” they published their results. They concluded that Bohr was wrong and that oxygen passed into the bloodstream by diffusion alone. This work led Krogh to believe that gas transport throughout the body relied on diffusion, and this belief proved an important factor in his subsequent studies on capillaries.

In 1910, Krogh started working with a professor of gymnastics, Johannes Lindhard, on muscular work in humans. Their experiments on the circulatory system showed the enormous increase in the total circulation rate induced by muscular activity. It also revealed that the increase in oxygen consumption occurred mainly in the working muscles. These results led him to question how the same circulatory system could satisfy the high oxygen demand of the body at work and the relatively low demand at rest.

The current theory on capillaries hypothesized that as the heartbeat quickened, the rising blood pressure forced open more and more capillaries in the muscles. Krogh found this theory unacceptable. During physical exertion, this system would open capillaries throughout the body, even where extra oxygen was not needed. Krogh started with the idea that every capillary, by supplying blood, supplied oxygen to the surrounding tissue by diffusion. He then asked how the capillary network could be sufficient for the body’s needs for oxygen during work without being wasteful during periods of rest. One day, while he was at the library, a solution occurred to him: If a local lack of oxygen in the muscle forced the opening of the nearest capillary, and a relative surplus allowed the capillary to close, the capillaries would open or close in alternation. This would allow for increased oxygen supply only where and when needed, serving equally well in times of relaxation or intense activity.

Now that he had a theory, Krogh had to determine if it was worthwhile to make an experimental test of it. He later said that nothing short of experimentation helped more to clarify his ideas than discussion with a sympathetic colleague. Thus, that evening he went home to discuss his theory with his wife. Jorgensen Krogh decidedly influenced her husband’s studies; Krogh himself described her as “always my nearest colleague.”

To test his hypothesis, Krogh needed to determine if increased oxygen demand did indeed result in the opening of more capillaries. He observed the tongue of a frog and found that, when stimulated, many more capillaries became visible as a result of being filled with blood. To answer the question of whether only the capillaries of stimulated muscles opened, however, he needed an alternative method; the capillaries from many parts of the tongue needed to be observed simultaneously. To do so, Krogh used an India-ink solution injected into the bloodstream shortly before death. Any open capillaries, filled with the mixture of blood and ink, would then appear as black lines. He found that capillaries of the skin, liver, and brain, organs that are constantly active, were always open. The empty stomach and intestine had only a small number of open capillaries. The muscles varied, with inactive muscles relatively white, while the ones stimulated before stopping circulation appeared almost black from the large number of injected capillaries. Obviously, then, the capillaries themselves had the ability to open or close as needed, allowing oxygen through their walls by diffusion, as Krogh had hypothesized.

Krogh published his findings in 1918. The significance of his work was understood surprisingly soon, and he received the Nobel Prize in Physiology or Medicine in 1920. However, while the publicity from this award attracted many scholars eager to work with him, Krogh himself remained in the background. Therefore, his students received the lion’s share of recognition from their researches, something in which Krogh strongly believed. In 1922, Krogh published a review of the research done by himself and his students, The Anatomy and Physiology of Capillaries , which represents his major contribution to medical science. After this, though his guidance was actively sought, and if rejected was done so foolishly, Krogh’s contributions to human physiology became secondary.

In his later years, Krogh returned to zoophysiology, his first love. In 1941, he published The Comparative Physiology of Respiratory Mechanisms , returning to his original work on oxygen exchange, but now including the insect world. Even after his retirement in 1945, Krogh remained active, beginning an investigation into the flight of insects. Only Krogh’s death in 1949 stopped his studies.

Significance

With the recognition that came with the Nobel Prize, Krogh’s laboratory attracted scholars from all over the world, especially the United States. At least twenty Americans spent time under Krogh’s direction, and in 1951, two years after his death, the faculty of Harvard University included eight professors who had studied with him. His students often remarked that their love for him was excelled only by their respect for his scientific ability.

The implications of Krogh’s research with oxygen diffusion through the capillary walls proved wide-ranging. The lymph system and the kidneys are affected by diffusion through the capillaries. Diffusion also accounts for inflammatory symptoms, such as allergy, edema (the swelling of tissues by fluid retention), and surgical and wound shock (hemorrhage). These areas and many more fell to Krogh’s students to pursue.

Krogh also used his fame to further humanitarian concerns. When in the United States in 1922 to deliver a series of lectures on his work on capillaries, Krogh acquainted himself with the preparation of the newly discovered insulin. On his return to Denmark, he organized its production and convinced the producer that it should be manufactured without profit. Thus this lifesaving substance could be obtained in his homeland at a much lower price than elsewhere only one of the many ways that Krogh advanced scientific studies in his native Denmark.

Bibliography

Drinker, Cecil K. “August Krogh: 1874-1949.” Science 112 (July 28, 1950): 105-107. Written by one of Krogh’s students, this recollection fondly describes what it was like to work in the Krogh laboratory. Drinker notes Krogh’s kindly direction and concern for his students.

Hill, A. V. “Schack August Steenburg Krogh, 1874-1949.” Obituary Notices of Fellows of the Royal Society 7, no. 19 (November, 1950): 221-237. An obituary by a scientific organization of which Krogh was a member. It includes a portrait of Krogh, a complete listing of his publications (almost three hundred entries), and excerpts from the speech given when he was awarded the Nobel Prize.

Krogh, August. The Anatomy and Physiology of Capillaries. New Haven, Conn.: Yale University Press, 1922. Reprint. New York: Hafner Press, 1959. Contains a reminiscence of capillary studies that Krogh delivered in 1946, explaining the influences that directed the research that resulted in his receiving the Nobel Prize. It also includes an annotated bibliography on capillary research.

‗‗‗‗‗‗‗. The Comparative Physiology of Respiratory Mechanisms. Philadelphia: University of Pennsylvania Press, 1941. Reveals the research interests that most compelled Krogh, the combination of oxygen exchange, and the respiratory systems of lower-order animals, especially insects. Includes illustrations of the exchange systems of many different animals, a listing of all animals investigated in the book, and an annotated bibliography.

Larsson, Ulf, ed. Cultures of Creativity: The Centennial Exhibition of the Nobel Prize. Canton, Mass.: Science History, 2001. This centennial history of the Nobel Prize includes a biography of Krogh.

Rehberg, Brandt P. “August Krogh: November 15, 1874-September 13, 1949.” Yale Journal of Biology and Medicine 24 (1951): 83-102. Written by Krogh’s research associate, this article is a wide-ranging account of Krogh’s career. Of note is its review of Krogh’s zoophysiological pursuits, especially in the years after he won the Nobel Prize, and his approach to laboratory work.

Schmidt-Nielson, Bodil. “August and Marie Krogh and Respiratory Physiology.” Journal of Applied Physiology 57 (August, 1984): 293-303. A daughter of the Kroghs recounts the Krogh family life, especially the close working relationship between her mother and father. She deals most extensively with August Krogh’s childhood and the early years of his research. The seven papers that proved the Kroghs’ oxygen-diffusion theory for the lungs are dealt with at length. Includes photographs.