"You've probably never heard of Dr. Yellapragada SubbaRow. Yet, because he lived, you may be alive and well today" (Doron K. Antrim wrote in Argosy in April 1950.)
These
were the words of a writer about an Indian scientists who remains unsung even
today in his own country. Dr. Yellapragada SubbaRow was born on January 12,
1895 in a village Bhimavaram in West Godavari (erstwhile Madras Province) in
the state of Andhra Pradesh, India. His initial years of schooling passed
traumatized as he witnessed deaths of his close relatives. He passed his
matriculation in his third attempt (exact source unknown). After passing
intermediate, he joined Madras medical college. Motivated by the call of
Mahatma Gandhi to boycott British goods, he started wearing khadi-made surgical
dress that was not accepted by his professors. Consequently, though he passed
his examination well, he was not awarded Licentiate of Medicine and Surgery
(LMS) certificate. He, therefore, could not obtain full MBBS. Because of lack
of LMS certification, he was debarred of Madras Medical Service and he had to
join Madras Ayurvedic College as a lecturer of anatomy and physiology. The
teaching and work ethics of Dr. SubbaRow were so impressive that he was
promoted as Vice-Principal of the college by the then principal Dr. Lakshmi
Pathi. Dr. John Fox Kendrick, who was a visiting doctor to the Madras Ayurvedic
College, noticed the talent of Dr. SubbaRow and advised him to join Harvard
School of Tropical Medicine. He joined Harvard School of Tropical Medicine for
a post-graduation in tropical medicine. With an aid of Rs. 1500 annually (from
MSN Charities) and some financial assistance from his father-in-law, Dr. SubbaRow
landed in Boston. He, however, could not obtain Harvard scholarship due to
incomplete LMS certification and he ended up working as night porter (cleaning
urinals and bed pans of patients) to support himself further. Luckily, after
successfully completing the course and obtaining a diploma (in 1924), Dr.
SubbaRow joined Harvard Medical School as a researcher under Dr. Cyrus Fiske. This
was the year when his son was born, but unfortunately succumbed to Erysipelas
(a form of cellulitis) within six months. The work assigned to him by Fiske was
accurate determination of phosphorus in bones, cells, and nerves. Gradually,
Dr. SubbaRow came in good books of Dr. Fiske and they developed Fiske-SubbaRow
method of determination of phosphorus in tissues and body fluids. The first
pathbreaking discovery made by Dr. SubbaRow was deciphering the role of
phosphocreatine and ATP in muscle activity that earned him an entry into the
textbooks of biochemistry. His research on phosphorus determination in cells
and tissues gained him a PhD in biochemistry in the year 1929. His research
article “The colorimetric determination of phosphorus” published in Journal of
Biological Chemistry has been cited more than 21000 times (one of the highest
cited paper in history). Even with such a profile that time, he was denied a regular
faculty position at Harvard, but continued as a teaching fellow at Harvard
medical School.
Nevertheless,
Dr. SubbaRow started his study of liver fractionates and isolation of factors
that could cure pernicious anaemia in 1927 (two years before he received his
PhD). Since he was denied a faculty position (and perhaps continued on a
temporary position) he was approached by major pharmaceutical companies such as
Merck and Lederle Laboratories. He joined Lederle as Director of Research at
New York (in 1940). He thought the company matched the level of research
enthusiasm that he had. His enthusiasm and dedication for research can be
witnesses from a short excerpt mentioned below
“The amusing condition he put forward was that instead
of $14,000 annual salary offered, he would accept half if a new research building
was constructed for him at Pearl River. SubbaRow later said to William
Berenberg that he was not concerned about the finances for personal benefits
but more for a chance to work at a modern research facility, without having to
be concerned about budgets”
Dr. SubbaRow, along with Fiske and Jacobson,
was successful in isolating anti-pernicious factor, which is now known as
Vitamin B12. His success did not take a halt here, but he also isolated
niacin (and found its therapeutic effect on pellagra), pantothenic acid
(Vitamin B5), and Biotin. Along with a few other researchers, he
successfully developed the method to isolate and synthesize folic acid (Vitamin
B9) in large scale that became a major profitable compound for
Lederle. Dr. SubbaRow was the brain behind discovery and development of
diethylcarbamazine (the first drug for filariasis) and this drug was listed in
the WHO list of essential medicines.
As the list of his research contribution is really long, for the sake of ease of remembering, I am putting them point-wise below:
- Discovered and isolated Pantothenic acid (Vitamin B5), Biotin, Niacin, Folic acid (Vit. B9), and Vitamin B12.
- Developed diethylcarbamazine, the
first drug against filariasis.
- Developed aminopterin for leukemia
treatment (assisted Dr. Sidney farber, father of modern chemotherapy)
- Discovered methotrexate, one of the
most widely used anti-cancer chemotherapeutic drugs.
- Discovered polymixin (one of the most
potent antibiotic; includes Polymixin B and E)
- Discovered tetracycline and
chlortetracycline antibiotic.
The story of tetracycline discovery,
as noted from the publication dedicated to the life of Dr. SubbaRow, is put
here in a short and inspiring manner. Dr. SubbaRow recruited Prof. Benjamin
Duggar (retired professor of mycology) for a research project on discovery of
novel antibiotics. They discovered the first tetracycline antibiotic
(chlortetracycline, named Auromycin since it was extracted from Streptomyces
aureofaciens). This team also developed Polymixin antibiotic. In Roosevelt
Memorial, Dr. SubbaRow took a backseat and let Prof. Duggar introduce the
antibiotic to the world. This is considered his last contribution to the world
as he left for heavenly abode on August 9, 1948 at the age of 53. On his death, the New York Herald‑Tribune addressed him
as "one of the most eminent medical minds of the century"
Dr. SubbaRow’s dedication for research
is truly evident from his numerous contribution to the field of medicine. The
use and efficacy of methotrexate for leukaemia surprised the world at that
period and replaced aminopterin (aminopterin had serious adverse effects).
Later, aminopterin underwent a clinical trial for psoriasis and was found to be
highly effective in treating the condition. Subbaromyces splendens, a
fungal species found in the Pearl river, was named after Dr. SubbaRow after his
death as a small token of appreciation (was that enough ??)
I find no words in appreciating Dr.
SubbaRow, but this short excerpt may tell a story itself
“SubbaRow never pursued fame, maybe because of his
disinterest in marketing himself and his reluctance to step into the limelight.
He never seemed to be interested in giving interviews to the press or taking
rounds of the academies or go on lecture tours. In his biography, Dr. S.P.K.
Gupta rightly says: “He was quite determined that the time allotted to him on
earth should be completely devoted to finding cures for ailments that plagued
mankind.”
“His efforts always seemed to be more focussed on
research than acquiring credit for it and his humble nature of sharing credit
with his junior researchers, who worked devotedly under his guidance, was
indeed a rare quality. The most enlightening thing about his life was the
amount of energy and enthusiasm he put selflessly in efforts for scientific
research and his devotion to medicine.”
Dr. Pushpa Mitra Bhargava, an eminent
Indian scientist and founder of CCMB Hyderabad, praised Dr. SubbaRow in his
article in Swarajya magazine
“Rarely, extremely rarely, a person comes on the world
scene and transforms science and our lives by making a large number of major
discoveries in – and otherwise makes important contributions to – more than one
basic field and does not only not get a Nobel Prize but does not get to be
known by name to most people, including scientists around the world.”
Dr. SubbaRow, despite having contributed
immensely to the medicine and humankind, faced hardships living in USA. A brief
mention can be read in the complete article by Dr. Bhargava (link in the
reference section, a must read). Though I found a few contradictory events
about his life during my research for this blog post, all the references have
been cited at the end for the readers to delve into the life of this great
unsung mind.
References
Bharti AH, Marfatia YS. Yellapragada
SubbaRow – The unsung Indian biochemist behind methotrexate and other drugs.
Indian J Dermatol Venereol Leprol 2017; 83: 733-5.
https://swarajyamag.com/science/yellapragada-subbarow-transformed-science-changed-lives
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