As early as the 6th century B.C. the Greeks speculated on a substance pneuma that meant breath or soul, and they argued that this was essential for life. An important figure in the 2nd century A.D. was Galen whose school developed an elaborate cardiopulmonary system that influenced scientific thinking for 1400 years. A key concept was that blood was mixed with pneuma from the lung in the left ventricle thus forming vital spirit. It was also believed that blood flowed from the right to the left ventricle of the heart through pores in the interventricular septum but this view was challenged first by the Arab physician Ibn al-Nafis in the 13th century and later by Michael Servetus in the 16th century. The 17th century saw an enormous burgeoning of knowledge about the respiratory gases. First Torricelli explained the origin of atmospheric pressure, and then a group of physiologists in Oxford clarified the properties of inspired gas that were necessary for life. This culminated in the work of Lavoisier who first clearly elucidated the nature of the respiratory gases, oxygen, carbon dioxide and nitrogen. At that time it was thought that oxygen was consumed in the lung itself, and the fact that the actual metabolism took place in peripheral tissues proved to be a very elusive concept. It was not until the late 19th century that the issue was finally settled by Pflüger. In the early 20th century there was a colorful controversy about whether oxygen was secreted by the lung. During and shortly after World War II, momentous strides were made on the understanding of pulmonary gas exchange, particularly the role of ventilation-perfusion inequality. A critical development in the 1960s was the introduction of blood gas electrodes, and these have transformed the management of patients with severe lung disease.