The Nature of Leukemic Blood Cells as Determined by Their Metabolism.

" The nature and etiology of leukemia are unknown " (1). Some authors (2, 3, 4, 5, 6, 7, 8) are in favor of classifying the leukemias as malignant neoplasms of the blood-forming organs, because of the formation of leukocytes in unaccustomed organs, the new growth of leukemic tissue, and the flooding of the blood stream with abnormal primitive cells. Others (9) prefer to consider leukemia as a type of benign tumor formation, or tissue metaplasia, or simply as an excessive, unregulated production and outpouring of essentially normal young tissue cells. To solve the problem by means of morphological histology has proved impossible (10). A new approach to this question was opened, however, by the methods of cellular physiology, and this paper presents experimental results obtained by these methods, which, it seems to me, give an unambiguous and definite answer to the question of the nature of leukemic cells. As Warburg (11) has found, cells of benign, and to an even greater degree of malignant tumors, differ fundamentally from normal cells in their energy supplying metabolic reactions. In all normal undamaged animal cells the magnitude of the oxidative metabolism is considerably greater than the magnitude of the glycolytic metabolism and, under aerobic conditions, no splitting of sugar into lactic acid (glycolysis) occurs. In the metabolism of benign tumor cells and even more of cancer cells, the respiration-glycolysis ratio is disturbed; the rate of glycolysis is high as compared to the rate of respiration and a great amount of lactic acid is formed under aerobic conditions. This aerobic glycolysis, however, may have a different origin; it can be produced, for example, by poisoning the cells with cyanide, carbon monoxide, or arsenious acid, by various injuries leading to the gradual death of the cell, or, in the more sensitive organs, simply by keeping the tissue in Ringer's solution instead of its own plasma. Aerobic glycolysis as such, then, is not specific for malignancy, but rather the fact that the cancer cell can live and grow by its persisting glycolytic metabolism under aerobic and anaerobic conditions, whereas aerobic glycolysis in injured cells is only a metabolic phase of their dying off. If, therefore, under physiological experimental conditions, the determination of the cell metabolism reveals aerobic glycolysis of zero, it is certain that the tissue examined is normal and not cancer tissue, whereas the positive finding of aerobic glycolysis need not be specific for cancer cells, but may characterize either cancer metabolism or the dying off of any tissue within or without the body.