Effects of a Low Lysine Diet on the Growth of Spontaneous Mammary Tumors in Mice and on the Balance in Man*

The dietary requirement for certain amino acids essential to normal nutrition has long been established. It remained for Osborne and Mendel to distinguish those essential for normal growth from those required for maintenance. Of the 22 known amino acids that in various proportions go to make up the complex structure of the protein molecule, some 9 or 10 must be supplied to the organism in the diet. The animal is not dependent for the remainder preformed in the diet. Osborne and Mendel clearly demonstrated that while lysine is a normal constituent of body proteins its requirement for maintenance in the ordinary wear and tear of adult tissues is minimal. However, the conditions for rapid synthesis of new tissue protein incident to normal growth greatly increase the requirement for this particular amino acid. In short, they found that if lysine in the diet of healthy growing rats was reduced to the lowest level required for maintenance of fully mature rats, growth ceased; when lysine was added to such diets, growth was resumed. Thus lysine was distinguished as essentially a growth factor. With these facts established for normal growth the question arose whether malignant tumors, which are characterized by a rapid synthesis of new protein, follow this same pattern. If the growth of neoplastic tissues can be retarded by restricting or eliminating the intake of these growth factors in the diets of the host a new weapon would be available for controlling these abnormal growths. This problem was first outlined by this writer in 1915 (2). As a preliminary to our investigation of this problem, a quantitative analysis was made of various types of malignant tumor tissue for their content in lysine and related amino acids. It was found that the yields of lysine, arginine, and histidine Were considerably higher than those obtained on hydrolysis of normal somatic tissue. At the time this work was carried out in 1915 no laboratory animals suitable for experimental work on this problem were available. In lieu of such desirable preliminary experiments on