Dr. Yellapragada Subbarow, popularly known as the "wizard of wonder drugs." He was a pioneering researcher and brilliant teacher who made extraordinary contributions to medical science. He is an Indian-American biochemist. Subbarow's achievements span a wide range of discoveries, from elucidating the function of adenosine triphosphate (ATP) as an energy source in cells to developing methotrexate for cancer treatment. His work remains remarkable, guided by his own philosophy, "I must win a name in the world; then only would life be worthwhile."
The name Yellapragada denotes descent from Yellanna, a minister in the royal court of the Nawab of Golconda in the 17th century. His ancestors served as revenue accountants under several Indian rulers until the 19th century. However, the family’s fortunes declined after Subbarow’s grandfather, Subbaraju, passed away, leaving his position insufficient to support the growing joint family.
Yellapragada Subbarow was born on January 12, 1895, in Bhimavaram, now in Andhra Pradesh, India. He was the third of seven children to Mr. Jaganathan and Mrs. Venkamma. He faced a difficult childhood marked by tragedy, including the death of his father.
From a young age, Subbarow was both rebellious and determined. At thirteen, he ran away with his cousin to Varanasi to sell bananas for a living, but he was brought back, and continued his schooling. Despite numerous challenges, including the trauma of his father’s death, Subbarow never lost hope. His mother’s selfless support enabled him to return to Madras for a third attempt at the matriculation examination at Hindu High School, which he finally passed.
Subbarow then joined Presidency College in Madras, completing the intermediate examination with distinction in mathematics. Spiritually inclined, he spent considerable time at the Ramakrishna Mission and even aspired to become a saint. However, his mother refused to give written consent, steering him instead toward a medical career.
In 1915, he enrolled at Madras Medical College with financial support from friends and Kasturi Suryanarayana Murthy, whose daughter he would later marry. During his college years, Subbarow, a true patriot, heeded Gandhi’s call to boycott British goods by wearing khadi. This displeased his Professor of Surgery, and despite his excellent performance, he was denied the MBBS degree and awarded the Licentiate of Medicine and Surgery (LMS) instead. His application to the Madras Medical Services was rejected due to his lack of a graduate degree.
Subbarow worked as a lecturer in the Departments of Anatomy and Physiology at Dr. Lakshmipathi’s Ayurvedic College in Madras, providing him a path into research in Ayurveda. He deeply believed in Ayurveda’s tridosha theory, which views health and disease as the harmonious interaction of Kapha (protoplasm, the fluid matrix for life), Pitta (internal thermomechanism, which regulates metabolism), and Vata (which controls neuromuscular activity, including sensations, thoughts, and emotional impulses).
Due to financial and resource constraints at the Ayurvedic College, Subbarow sought opportunities in the United States.
Tragedy struck when his elder brother Purushotham, who was arranging a travel scholarship for Subbarow, died of a sprue-like illness. Just a week later, his second brother, Krishnamurthy, also succumbed to the same illness. Their deaths inspired Subbarow to research therapies for these devastating diseases. With financial assistance from his father-in-law, Kasturi Surya Prakasha Row, he traveled to Boston on October 26, 1922.
In Boston, Richard Strong, Director of the Harvard School of Tropical Medicine, provided Subbarow with financial support, laboratory facilities, and a scholarship. To support himself, Subbarow worked odd jobs, including cleaning bedpans.
He graduated with a Diploma in Tropical Medicine in 1924 and then enrolled in Harvard Medical School for a PhD in Biochemistry, joining as a junior faculty member. His research mentor was Associate Professor Cyrus Hartwell Fiske, under the department led by Otto Folin.
Subbarow made several groundbreaking contributions to biochemistry, medicine, and pharmacology. He discovered ATP as a vital energy carrier in cells, which is often called the "energy currency" of the cell. ATP facilitates numerous cellular processes, including muscle contraction and metabolism. This research earned him a PhD and laid the foundation for modern biochemistry, cited in textbooks worldwide.
Subbarow developed a method to synthesize folic acid (Vitamin B9), essential for DNA synthesis and repair. This work was pivotal in treating nutritional deficiencies, especially tropical sprue, which was common in India, and in preventing anemia. His contributions transformed folic acid into a widely used therapeutic agent.
Subbarow also contributed to the development of methotrexate, one of the first effective chemotherapy drugs. Working with Dr. Sidney Farber, he helped create this antifolate drug, which slows cancer cell growth and is used to treat leukemia, lymphoma, and other malignancies. This was a major breakthrough in oncology.
At Lederle Laboratories, Subbarow led research resulting in the discovery of chlortetracycline, the first tetracycline antibiotic, in 1945. Guided by Subbarow, Benjamin Duggar developed this groundbreaking drug, first used successfully at Harlem Hospital in New York. Its success was so notable that some attempted to steal it from warehouses. Tetracyclines revolutionized bacterial infection treatment and remain essential in medicine today.
1950: Though his work was groundbreaking, Subbarow did not receive the Nobel Prize. His portrait was displayed at The Karolinska Institute in Stockholm.
1953: The fungus Subbaromyces splendens was named in his honor.
1967: Another species, Subbaromyces aquatica, was named at Osmania University, Hyderabad.
1995: The Indian government issued a postal stamp commemorating his centenary.
Despite his critical role in discovering folic acid and malaria treatments, Subbarow often remained uncredited, with many awards going to others. Financial and institutional hurdles frequently complicated his research. His colleague George Hitchings later admitted, "Some of the nucleotides isolated by Subbarow had to be rediscovered years later by other workers because Fiske, apparently out of jealousy, did not let Subbarow's contributions see the light of day."
Despite these challenges, Subbarow’s perseverance was extraordinary.
Subbarow passed away on August 8, 1948, in New York due to cardiac arrest at the age of 53. His immense body of work continues to save lives worldwide. As Doron K. Antrim wrote in the April 1950 issue of Argosy, "You've probably never heard of Dr. Yellapragada Subbarow. Yet because he lived, you may be alive and well today. Because he lived, you may live longer."
Today, a street in his hometown of Bhimavaram bears his name, a small but fitting tribute to a man whose contributions to humanity were immeasurable.
References:
1. Sharma M, Choudhari SG, Ingole A. Yellapragada Subbarow: A Pioneer in Biomedical Research and the Unsung Hero of Modern Medicine. Cureus. 2024;16(8):e67442. Published 2024 Aug 21. doi:10.7759/cureus.67442
2. R N, Pragya V, Ramaswamy S, B N S, Mamadapur M. The Life and Discoveries of Yellapragada Subbarow. Digital Journal of Clinical Medicine. 2024; 7(1): -. doi: https://doi.org/10.55691/2582-3868.1221