A Letter from Ananda S. Prasad, MD, PhD, to the APS Distinguished Physiologists, January 2020
I was born in a small town in Bihar, India. At age four, I suffered from typhoid fever and almost died because there was no treatment available at that time. At age five, a severe earthquake hit our town but luckily, we survived. A year later, I witnessed a severe flood.
I graduated from high school at the age of 14 and received BS honors in mathematics at age 18. I joined Patna Medical College, Patna University, Bihar, India and received my MB, BS degree with distinction in Physiology in 1951.
I had a very sad experience at age 11 when my father passed away. I felt that my world had ended and I went into depression. My brother, who was 20 years older than I was, noticed my depression. He assured me that he was my second father and that he would take care of me. He was a great human being and he truly meant what he said.
India became independent in 1947. Until then the medical graduates from India went to England for their higher education and training.
Fortunately, for me AMA decided to accept 40 highly selected Indian physicians for training in USA. I was one of those selected in 1952. I went to St. Paul’s hospital in Dallas Texas for residency training in Pathology.
In 1953, I was fortunate to be accepted by Dr. C.J. Watson, a well-known outstanding Professor of Medicine at the University of Minnesota Medical School for training as a clinical scientist. Dr. Watson was an excellent teacher, a superb investigator and well-known physician. I worked under his guidance for five years.
I learned biochemistry, received my clinical training in Internal Medicine and Hematology and received a PhD in medicine and physiology in 1957.
As a resident physician, I studied and published the case of an unusual patient who was a 30 year old female, who had repeated episodes of pneumonia and meningitis and had hepatosplenomegaly and lymphadenopathy. This subject also had agammaglobulinemia. Bruton reported earlier, description of agammaglobulinemia in young males only. Our patient was an adult female and turned out to be the first example of acquired agammaglobulinemia.
Her bone marrow examination showed extensive reticulum cell hyperplasia but there were no plasma cells. We hypothesized that due to unknown mechanism, the reticulum cells stopped producing plasma cells and this resulted in agammaglobulimia. Reactive hyperplasia of reticular cells resulted in enlarged lymph nodes, hepatosplenomegalay and hypersplenism. Soon after our report, 18 cases of acquired agammaglobulimia were published all over the world.
Weil and Prasad published the syndrome of polycythemia of obesity in 1957. Other investigators published the same syndrome and they designated this as Pickwickan syndrome.
In the fifties, patients who underwent prolonged anesthesia during surgery used to develop hypotension, ventricle arrhythmia, shock, and even death after the surgery was completed and these events happened during early post hypercapnia phase. It was known that serum potassium would increase because of respiratory acidosis but this level of hyperkalemia was not considered lethal.
We conducted experiments in dogs. We either subjected the dogs to 30 minutes of respiratory alkalosis by over-ventilating with a positive pressure pump or exposed them for 30 minutes to inhalation of 30% Coշ in Oշ resulting in respiratory acidosis. As expected, ultrafiltrable calcium (ionic calcium) decreased during hyperventilation and increased during respiratory acidosis. After 4 h of prolonged respiratory acidosis, however we observed a sharp decrease in ultrafiltrable calcium. A rebound decrease in the ultrafiltrable calcium during the recovery phase of respiratory acidosis also occurred in every case. We also observed that plasma phosphate concentration increased during prolonged respiratory acidosis and we postulated that increased phosphate-protein complex bound calcium, which resulted in a significant decrease in ultrafiltrable calcium in post hypercapnia phase. It is during this phase that we observed cardiac arrhythmias, shock and death in dogs. The increased serum potassium levels and decreased ultrafiltrable calcium levels were detrimental to the cardiac contractibility, which resulted in cardiac arrhythmia.
Clowers Jr. and Simeone from Cleveland clinic, in patients who underwent prolonged anesthesia and surgery quickly confirmed these observations in the dogs. This led them to infuse calcium chloride in post hypercapnia phase and this resulted in preventing these serious fatal complications in humans. It is now a common procedure to use intravenous calcium infusion in patients who undergo prolonged anesthesia.
A strange set of circumstances took me to Shiraz, Iran in 1958. I went there to help Prof. Hobart Reimann who was Chief of Medicine at Jefferson, Philadelphia, and then went to Iran to set up a medial curriculum, patterned after an American Medical School at the Shiraz Medical School. Prof. Reiman was a friend of the Shah of Iran.
Within two weeks of my arrival in Shiraz, the Chief Resident of Medicine presented me a case at the Medical Center Grand Round. The patient was a 21-year-old male who looked like a ten-year-old male. He was extremely growth retarded, had hypogonadism, had no secondary sexual characteristics, had hepatosplenomegaly, and severe iron deficiency anemia but no blood loss. Extreme iron deficiency anemia in adult males without blood loss is very rare. Dietary history indicated that this patient ate only bread with some vegetables and had no intake of animal protein. Additionally he consumed one pound of clay (geophagia) every day.
Iron deficiency does not affect growth and development. We hypothesized that high phosphate intake from bread and clay may have affected iron absorption. Zinc was known to affect growth of plants, microorganism and rats. Thus, deficiency of both iron and zinc would account for severe anemia, growth retardation and hypogonadism. High phosphate was known to decrease also zinc absorption.
I subsequently joined Vanderbilt University and went to US Naval Medical Research Unit No.3 in Cairo, Egypt, where I studied zinc metabolism in growth retarded dwarfs in Egypt. Our studies established that zinc was essential for humans for growth and development. Zinc supplementation corrected growth failure and normalized gonadal development.
Our findings remained controversial until 1974 when National Academy of Sciences Research Council declared that zinc was an essential element for humans and their recommendation led US Congress to establish Recommended Dietary Allowance (RDA) for zinc for the American population. The impact of this discovery on human health has been phenomenal.
Zinc’s therapeutic roles in management of sickle cell disease, Wilson’s disease, acute diarrhea, and pneumonia in infants and children, as well as in prevention of blindness in dry type macular degeneration are now well known. The American College of Physicians highlighted my research as one of their top six physician scientists in 100 years whose work impacted greatly in medicine. American Physiological Society (APS) during their 125th year celebration honored 35 members for significant impact in Physiology and I was included in this group.
I have received many recognitions for my research contributions. These include, an Honorary Doctorate from Claude Bernard University of Lyon, France, membership in the European Academy of Sciences, Arts, and Humanities, received the Medal of Honor from the Mayor of Lyon, the prestigious Prince Mahidol Award from the king of Thailand, Mastership and Outstanding Award in Medicine from American College of Physicians for contributions in science related to medicine and received the Albert Nelson Lifetime Achievement Award by Marquis Who’s Who. Recently the American College of Physicians has established an annual lecture, The Ananda S. Prasad lecture in Medicine and Physiology, to be delivered annually at the College meeting.
I came to Wayne State University Medical School in 1963. I was appointed as Director of Hematology Division and Assistant Professor of Medicine. I was promoted to Associate Professor in 1964 and as a tenured Professor of Medicine in 1968. My Chief of Medicine was a famous Cardiac Physiologist, Richard J. Bing, who appointed me a Director of Hematology Division. Once I joined him, I asked him if he had any plans for me. He told me that I was free to do anything I wanted to as long as I remained creative. This was a great message!
I established a Hematology Fellowship Program, became Founding Editor of the American Journal of Hematology, and did several important studies in the field of hematology. We described Fibrinogen Detroit, a genetic disorder due to a single mutation in α (A) chain of fibrinogen molecule. Our studies established that sideroblastic anemia in young children was due to an x-linked genetic disorder. Our studies showed that zinc deficiency was commonly present in patients with sickle cell disease and Cochran Review reported that zinc supplementation was the only therapeutic modality, which decreases the incidence of infections and decrease pain crises in sickle cell disease patients.
I was appointed Distinguished Professor of Medicine in 2000 and became Director of Research in the Department of Medicine in 1998-2010. I continued my research and I am still involved in active research. We showed that zinc was essential for the activity of thymulin, a thymic hormone that was essential for T helper cells proliferation and differentiation. We reported that zinc was essential for generation of mRNA of IL-2 and IFN-γ and that zinc was essential for cell-mediated immunity. Currently in collaboration with Chris Frederickson, PhD. I am involved in developing Biomarkers of zinc deficiency in human and NIH supports this study.
I had many successes but also many frustrations in my life in Academic Medicine. In spite of this, I enjoyed every day of my life as a clinical scientist. Money was never my goal in life. Scientific contributions were my primary goal.
As I grew older, I experienced age discrimination in my pursuit of academic efforts but I tried to survive.
I married my loving classmate and friend in the medical school and I have four children and nine grandchildren. In 2017, I also lost half of my vision due to uncontrolled glaucoma. I suffered immense grief also in 2107 when I lost my only son who was an active and kind physician in medical practice. He died suddenly while exercising on a treadmill. I have not recovered from this shock but I also know that I must continue to live.
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