Strange set of circumstances took me to Shiraz Medical School, Shiraz, Iran in June 1958 after I finished my training as a clinical scientist and received a Ph. D. from University of Minnesota. Within a few weeks of my arrival, the chief resident of medicine at the Shiraz medical school presented to me a 21 year old male who looked like a 10 year old boy. He was extremely growth-retarded, had severe male hypogonadism, was severely anemic, had big liver and spleen and he gave a history of consuming one pound of clay (geophagia) every day. Later I learned that geophagia was very common in that part of the world amongst the villagers. Their diet consisted of only bread made of unleavened wheat flour, a few vegetables and fruits but he had no animal protein intake. It appeared that this syndrome was fairly common in the villages around Shiraz. The anemia was due to iron deficiency. I speculated that high phosphate content of the diet may have chelated iron and made iron unavailable for absorption and resulted in severe anemia in asmuch as there was no evidence of blood loss. I suspected that perhaps another element may also have been chelated by phosphate which could account for severe growth-failure. After examining the periodic table, I picked zinc as the other element being affected adversely by his diet and geophagia. It was known that zinc was a growth-factor for microorganisms, plants and rats but it was not recognized to be essential for humans. Assay of zinc in plasma and human tissues by dithizone technique was extremely difficult and I was unable to get plasma zinc assayed anywhere in the world.
In the first paper which we published in 1961 in the American Journal of Medicine, I speculated that perhaps growth-retardation and hypogonadism in these cases were due to zinc deficiency. This paper became a nutrition classic and also a citation classic several years later.
This paper attracted the attention of many clinical scientists in USA and one of them, Prof. William J. Darby, Professor and Chief of Biochemistry Department at Vanderbilt University, Nashville, Tennessee invited me to meet him at United States Naval Medical Research Unit No. 3 in Cairo, Egypt, in order to discuss the possibility that zinc deficiency was a major problem in the Middle East, accounting for growth-retardation in this region. This idea was very attractive to me and I accepted Dr. Darby’s offer and moved to Cairo, Egypt. I received adequate support from Vanderbilt University, US Navy and NIH. My first objective was to study zinc metabolism in these dwarfs and determine if zinc deficiency occurred in humans.
We published in 1963 our second paper showing conclusively that zinc deficiency occurred in humans. We assayed zinc in the plasma, red cells, hair and urine by the difficult dithizone technique and with the use of Zn65 we assayed 24h exchangeable pool of zinc and plasma zinc turnover rate. This paper was the first to document human zinc deficiency. It became a citation classic, nutrition classic and was republished as a Landmark article.
The American Physiological Society (APS) recognized the achievements of their members during the past 125 years at the 2012 annual meeting. APS members whose publications significantly advanced the discipline and profession of physiology were recognized. Thirty-five members were selected for the honor. I was included in this list for my original publication of zinc as an essential element for the humans.
In 2015, The American College of Physicians highlighted my contributions in zinc area and included me as one of their top six physician scientist in 100 years whose work impacted greatly in the field of medicine.
Our next important observation was that zinc supplementation alone resulted in height gain of five to six inches in one year and sexual development became adult like within three to six months. They remained anemic. Those subjects who received only iron corrected their anemia but nothing happened to their growth or gonadal development. These results were truly astounding as we had never seen anything like this described in the literature.
Prasad, A.S., Miale, A., Farid, Z., Sandstead, H.H., Schulert, A. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypogonadism. J. Lab. Clin. Med., 61:537‑549, 1963.
Sandstead, H.H., Prasad, A.S., Schulert, A.R., Farid, Z., Miale, A., Bassily, S., Darby, W.J. Human zinc deficiency, endocrine manifestations and response to treatment. Am. J. Clin. Nutr., 20:422‑442, 1967.