been realized in part because he was the first to recognize the need to individualize dietary therapy in patients, in order to gain the benefits of a low-protein diet without incurring an excessive risk of protein malnutrition.

ORGAN GROWTH AND HYPERTROPHY (1925-49)

As in earlier work on the regulation of renal activity and the rate of urea excretion, much of Addis's work on organ growth and hypertrophy was reported in a large series of papers on factors that determine renal weight. Addis was not an author of all twelve papers in this series. Much of his work on the topic was conducted in collaboration with Eaton and Lois MacKay, William Lew, Lee J. Poo, and Horace Gray.

With the development of the concept of therapeutic rest, a reliable index of renal work was needed. Although the thermodynamic definition of renal work played a major theoretical role, it also had limitations. The idea of organ weight as an indirect measure of organ work was therefore exploited. The use of change in organ weight to reflect work was supported by an analogy with the increase in muscle mass that results from sustained increases in muscle work.

In order to utilize this approach, organ weights had to be normalized for age, sex, and diet, and the relationship between organ weight and body weight (or surface area) had to be established. Weights of different organs under specific "stresses" were examined: hypertrophy of the gastrointestinal tract under conditions of increased dietary bulk (increasing the work of moving material through the tract), changes in the weight of paired organs after removal of one of them, and changes in organ weights following alterations in overall metabolism (thyroidectomy, thyroid hormone administration, pregnancy). In the kidney the ef-



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