Online Supporting Material Supplemental Figure 1.

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1 Supplemental Figure 1. Ananda S Prasad, MD, PhD, the first to suggest that zinc deficiency was the cause of stunting and hypogonadism among Iranian farmers, and later, the first to show his hypothesis true (2-8). Reproduced with permission from (1).

2 Supplemental Figure 2. James A Halsted, MD (10), the collaborator of Ananda Prasad who asked him to evaluate the Index Case (2). Later, Halsted et al (11) confirmed the findings from Egypt that showed zinc deficiency caused stunting and hypogondism. Reproduced with permission from(10).

3 Supplemental Figure 3. The Index Case the first patient described by Prasad that was presumed to be zinc deficient. Reproduced with permission from (2).

4 Supplemental Figure 4 William J Darby, MD, PhD, Director of the Vanderbilt Nutrition Group (VNG) at NAMRU- 3. He recognized the potential importance of Prasad s Syndrome and therefore added human zinc deficiency to the research agenda of the VNG. Reproduced with permission from (12).

5 Supplemental Figure 5. Arnold E Schaefer, PhD Executive Director of the Interdepartmental Committee for National Development (14) based at the National Institutes of Health. He gave permission to expend funds to test Prasad s Hypothesis. Reproduced with permission from (13).

6 Supplemental Figure 6 Comparison of height of Iowa school boys relative to age, to height and bone age relative to chronological age of zinc deficient male farmers from the Nile delta of Egypt ). Stunting was severe. With few exceptions, stature was more affected than bone age. Reproduced with permission from (9)

7 Supplemental Figure 7 Hypogonadism in a 16 year stunted farmer for the Nile delta of Egypt (9). Juvenile genitalia such as shown here were present in all 56 of the zinc deficient farmers from the Nile delta and 2 desert oasis (4-9). Photograph by Harold H Sandstead.

8 Supplemental Figure 8 Growth of a zinc deficient stunted farmer from the Nile delta while living at home, during treatment at NAMRU-3 with diet alone, or diet and zinc. The subject was at home for 279 days. He returned to NAMRU-3 and was treated for hookworm, and fed the diet for 41 days. He was then treated for 88 days with diet and zinc. His calculated 1-year growth increment was nearly 17.8 cm. Reproduced with permission from (9)

9 Supplemental Figure 9. The effect of diet and zinc treatment on growth and development of a zinc deficient farmer, aged 17 years, from the Nile delta. Treatment with diet and zinc while living in the metabolic unit of NAMRU-3 was associated with increased growth and genital development. From to he grew 7 cm. From to his penis and scrotum began to mature. Pubic hairs were evident on Reproduced with permission from (9)

10 Supplemental Figure 10 The effect of diet and zinc treatment on growth and development of a zinc deficient farmer, aged 20 years, from the Nile delta. Treatment with diet and zinc while living in the metabolic unit of NAMRU-3 was associated with increased growth and genital development. From to he grew 5 cm. Pubic hairs were evident on Reproduced with permission from (9)

11 References 1 Proceedings of the Fifty-Eighth Annual Meeting of the American Institute of Nutrition: Anaheim, California April 24 April 28, J. Nutr. 1994; 124: Halsted JA, Prasad AS. Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Trans Am Clin Climatol Assoc. 1960;72: Prasad AS, Halsted JA, Nadimi M. Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med. 1961;31: Prasad AS, Miale A, Jr., Farid Z, Sandstead HH, Schulert AR. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypognadism. J Lab Clin Med. 1963;61: Prasad AS, Miale A, Jr., Farid Z, Sandstead HH, Schulert AR, Darby WJ. Biochemical studies on dwarfism, hypogonadism, and anemia. Arch Intern Med. 1963;111: Prasad AS, Sandstead HH, Schulert AR, El-Rooby AS. Urinary Excretion of Zinc in Patients with the Syndrome of Anemia, Hepatosplenomegaly, Dwarfism, and Hypogonadism. J Lab Clin Med. 1963;62: Prasad AS, Schulert AR, Sandstead HH, Miale A, Jr., Farid Z. Zinc, iron, and nitrogen content of sweat in normal and deficient subjects. J Lab Clin Med. 1963;62: Prasad AS, Schulert AR, Miale A, Jr., Farid Z, Sandstead HH. Zinc and iron deficiencies in male subjects with dwarfism and hypogonadism but without ancylostomiasis, schistosomiasis or severe anemia. Am J Clin Nutr. 1963;12: Sandstead HH, Prasad AS, Schulert AR, Farid Z, Miale A, Jr., Bassilly S, Darby WJ. Human zinc deficiency, endocrine manifestations and response to treatment. Am J Clin Nutr. 1967;20: Smith JC, Swendseid M. James A. Halsted. J Nutr. 1988;118: Halsted JA, Ronaghy HA, Abadi P, Haghshenass M, Amirhakemi GH, Barakat RM, Reinhold JG. Zinc deficiency in man. The Shiraz experiment. Am J Med. 1972;53: Sandstead HH, Wagner C. William J. Darby, J Nutr. 2002;132: Combs GF. Arnold Edward Schaefer ( ). J Nutr. 1993;123: Sandstead HH. Origins of the interdepartmental committee on nutrition for national defense, and a brief note concerning its demise. J Nutr. 2005;135: