Yellapragada SubbaRow – A Great Man of Science

Relentless in the pursuit of cures

North of Guntur in Andhra Pradesh where it's famed red-hot chilies grew, and South of Rajamundry where many a graceful courtesan of yore was trained is situated a sleepy little village, named Bhimavaram, the name literally meaning "the gift of Bhima". Bhima means giant, as you all know. Legends tell us that around 890–918 AD, a Chalukya king named Bhima built a Siva temple and laid the foundation to this town, which thence carried his name. Legends and lore have faded away, leaving just Bhima’s name behind. This was the village blessed by the birth, in 1895, of a little boy named Subbarao (fourth among seven siblings) to Jaganatham and Venkamma. This little boy, Yellapragada SubbaRow, would go on to become a giant, yet another Bhima, in his field of expertise.

To a certain extent, he was a confused man in his teens, wanting only to make a name for himself, then wanting to become an ascetic monk, which he forsook (his mother Venkamma refused permission) to thence follow a career in medicine. When he first ran away from home, aged 13, with his cousin to Varanasi, the boys had planned to sell bananas to pilgrims in order to make a living. They were caught and brought back, and schooling continued, but Subbarow made a few attempts to pass his matriculation. Nationalism was on the rise and for a while, that fervor took a hold of him, due to which his stentorian mother sent the boy off to Triplicane in Madras to continue his high school. Tragedy struck, as his father who had not thrived as a revenue officer, succumbed to beriberi. But the boy passed his exam on the third attempt. Though he drifted toward the Ramakrishna Mission for a while against his mother’s wishes, Subbarow passed his intermediate, with distinction in Maths. Eventually, he joined the MMC Madras Medical College, in 1915.

Somehow, in the middle of his medical studies, he got married to a very young child bride Sheshagiri, and obtained some financial support from his father-in-law, a prosperous agriculturist. It was a personal affliction and tragedy which led him into Ayurveda. Acute dysentery caused by tropical sprue laid waste two of his brothers and nearly took his life too, as allopathic medicines failed to help. Ayurvedic treatment cured him and got him interested in that line of medicine for a period, but as you guessed, he drifted on, still in search of his future. Apparently, due to his nationalistic fervor and wearing khadi clothes, Subbarow was failed his surgery exams by the British professor and thus obtained only an LMS certification, not an MBBS degree.

A chance meeting with an American doctor John Fox Kendricks, convinced him that his future lay in America, and Row applied to the Harvard Medical school of tropical medicine and got admission, but then found that finances were impossible to come by and a scholarship hard to get, especially so since his brother who could have helped with the necessary recommendation, to the philanthropist, Satyalinga Naicker’s charities had passed away after contracting sprue. With no other avenues open, he accepted the post of a lecturer in the Madras Ayurvedic college at a Rs 70/- monthly salary.  He kept at it, spending time on a pet project of codifying available knowledge on Ayurveda, into a tome.

His efforts to go to America continued and his application to Harvard again bore fruit, but the US university informed that research in Ayurveda was not something up their avenue. They also made it clear that a scholarship was not available. Somehow, with the help of his father-in-law and another friend, Row managed to scrape enough finances for the forthcoming voyage to Boston. One thing was clear though, the young wife Sheshagiri would remain in India while at the same time, the prospect of Row’s return to India seemed bleak (even though he promised to return in 3 years). Row was on his way, and the sailing on the P&O liner SS Kashgar to Boston via London, uneventful. Interestingly, he had prepared for the voyage and in order to combat seasickness, he practiced the motion on a swing for many days, near his home.

SubbaRow disembarked in Boston on 6^th Oct 1923 and joined the course for tropical medicine with some financial support from Dr RP Strong, his mentor as well as an anonymous doctor. His certificate from Madras was not good enough to get him a job in any hospital, and the only job he could get was as a night porter at the Bringham hospital, washing urinals and bed pans every night, and living in the dark basement of a nearby building. Though Dr Strong tried hard to get him another job, he was unsuccessful, perhaps due to the young Indian’s color and lack of acceptable qualifications. All he could do was to give him flexibility for his classes in parasitology. That research led SubbRow to study in-depth E-Coli, Filariasis and Trypanosomiasis. By the end of the year, he heard glad tidings that a son was born to him in India. Eight months later, he obtained his diploma in tropical medicine.

Some people even though eminently qualified in the fields of science tend to be superstitious and SubbaRow too was no different, he was sure his son would die in his infancy and kept writing home trying to get his family to come to terms with the impending doom. As he prophesied, the child died in 9 months of a streptococcal infection. What SubbaRow did was to send some instructions and a kit to the Kings institute in Guindy, so that they can use it for such a future case of infection, if anybody contracted it.  A few days later, he lost his night porter job, but received the scholarship from India which he had been waiting for, and joined up for Biochemistry at Harvard. This was good enough for his tuition, and around the same time, a benevolent American in New York arranged a $30 per month stipend for his subsistence.

His relationship with his supervisor was to turn his life around, the person being Dr Cyrus H Fiske. Folin the department head managed to get him instated as a regular graduate student, with a part-time job as a library assistant. As luck would have it, he obtained a scholarship while the MSN charities in India doubled his scholarship. With a little savings, he purchased a secondhand microscope, and his barebone living continued.

Life went on smoothly, SubbaRow made some friends, Finke being one of them. He became somewhat of an eccentric at college with a reputation of being adept at his work. His first original work was the submission of a paper with Fiske on the method of estimating phosphorus in the human body, something very important to diagnose many diseases. In 1925, the colorimetry procedure was successfully demonstrated, and the Fiske-Subba Row method became the standard, to this day! Their next brilliant success in 1927 came when researching insulin effects on blood sugar, and the presence of phosphorous compounds in muscles. Eventually they discovered phosphocreatine and detailed how this agent controlled muscular action. It was revolutionary, for just a few years ago another (incorrect) hypothesis had won the scientists Myerhoff and Hill, a Nobel prize. Two lobbies formed, one supporting the erstwhile prize winners and another for the Fiske Row discovery. In addition to that, the Eggleton couple published their discovery of a similar phosphorous compound just two months before Fiske and SubbaRow could do it. A period of intense rivalry and determination of the compound continued between these parties and it appears that the discovery of ATP was eventually credited to K Lohmann from Myerhoff’s lab (Those interested in the details may peruse - The Discovery of Adenosine Triphosphate and the Establishment of Its Structure: Koscak Maruyama).

SubbaRow (as he chose to spell his name) was by now getting noticed and becoming famous, fellowships followed, and his earnings increased. With the newfound confidence and a fatter purse in his pocket, SubbaRow plunged into the American way of life. But two things made him plan an exit from Harvard, one being covert racism and the other being a lack of proper remuneration. Even years after his brilliant discoveries, he, a PhD holder (obtained it in 1930) was at the bottom rung of the ladder, working as a teaching fellow, a position usually reserved for graduate students. Even Folin’s persistent attempts could not break the prejudice, for example, he, a colored man would not be allowed to teach female students, at that time!

At this juncture, Folin passed away and Fiske angled for a promotion to fill Folin’s post. To boost Fiske’s chances, it appears that SubbaRow wrote a letter to the dean stating that all credit for the previous inventions were fully Fiske’s and that he was just helping Fiske. It did not help Fiske and an outsider Dr Hastings was brought in, while Fiske was awarded full tenure and SubbaRow, left in the cold got nothing. His experiments with Nicotinic acid had not been going quite well, nor did his collaboration with other universities. His teaching stint with a small promotion did not work out, students complained they could not understand his accent. Harvard later tried to explain their shoddy treatment of the brilliant young man, stating that he was offered limited opportunities only because he had a time-bound visa at that juncture, and that this uncertainty prevented them from offering him a proper faculty position.

But there was a little consolation, for a lady had entered his life – Vilma Prochownick, from Germany, as a research assistant. He would tell her often of his racial inadequacy on the America of the 20’s, of his thoughts on returning to India, and of a planned future away from Harvard, hopefully with her. This was not to happen, as Vilma contracted TB and was sent off to a sanitorium for a while, where she decided that science was no more her passion, but that literature was. WWII had broken out, her parents in Germany could no longer support her and she was hellbent on working in a library, to be among books! The two of them finally parted ways. Meanwhile, Sheshagiri in India was waiting for her husband who had no plans to return. He would write to her and send her money, but all she wanted was him to come home. Th three years had by now extended to seventeen years.

Lederle - Pearl River

Racial prejudices were a continuous problem and in one instance, he was arrested and held overnight when a lady in the neighborhood got molested. Around this time, in 1940, Lederle with whom he had collaborated while working on precocious Anemia and liver extracts, offered him a regular position with earnings of $15,000 as against the measly $2,700 Harvard was paying him. Joining Lederle, his responsibilities took a new turn, synthesizing vitamins and negotiating patents, as well as managing around 300 scientists. As years passed by, he concentrated on folic acid (part of the vitamin-B complex), helped develop its derivatives, teropterin and aminopterin (now being used to fight cancer), directed research that produced the new broad-spectrum antibiotic, aureomycin (a cure for serious infections untouched by penicillin or streptomycin). He also laid the foundations for the isolation of vitamin B12.

One of his important discoveries was the cure for filariasis using two-ethyl compounds. I guess in many ways, he was the reason many hundreds in Kerala were cured of this terrible ailment, especially those residing near the canals and rivers and toiling in cottage coir industries.

His collaboration with Dr Sydney Faber in using teropetrin for chemotherapy against cancer are legendry and explained in detail in Siddhartha Mukherjee’s lovely book The Emperor of All Maladies: A Biography of Cancer.  At Farber's request, SubbaRow's team developed a series of antifolates (folic acid antagonists), including aminopterin, and found that these disturbed the metabolism of leukemic cells in chickens and mice, an effect that could then be reversed by administering folic acid. It was rumored that SubbaRow’s next project would be to find a cure for cancer and his associates were sure he would succeed.

Sadly, it was not to be, YSR, Sub or SubbaRow as people addressed him, aged just 52, passed away in his sleep, due to natural causes on Aug 9th, 1948. An autopsy pointed to a heart attack. Poignantly, his mother Venkamma outlived him for 41 years, to a ripe old age of 94. After SubbaRow’s death, his pastor Merton Lockhart, held onto his ashes, with no plans to send it to India for a Hindu disposal, believing them to be inconsistent with Baptist beliefs and the confidence that SubbaRow had accepted Christian beliefs.

Along the way he posed like most Americanized Indians but he was still not a naturalized citizen. Until 1946, America did not permit people of Indian origin to apply for American citizenship even though Caucasians and Chinese could! In 1946, PL 483 passed by President Truman allowed Indians to apply for American citizenship. SubbaRow processed his papers and obtained the necessary clearance, but failed to go through the next step, of submitting a declaration of intent.

SubbaRow had varied tastes, he learned how to swim, ride horses, shoot arrows and fly planes. He developed an interest in orchids and was trying to figure out how he could get them to grow faster. He learned to fly on an Aeronca biplane, mostly to relieve work tensions, and flew a long distance just three days before his death.

A few years after Subba Row’s death in 1948, Lederle laboratories opened a plant in India at Bulsar near Bombay. A plaque was unveiled, stating: “Science simply prolongs life—Religion deepens it.” The Lederle plant in Bulsar symbolized Dr. Subba Row’s scientific contributions made to the United States and India. As was stated, many of the pharmaceuticals produced under his direction have improved the quality of life for people in both countries and for millions of others around the world.

While SubbaRow was indeed a meticulous scientist and researcher, his personal side is not very well known to the public, so I thought I’d spend few paragraphs on SubbaRow, the person. The eulogies and the two or three biographies are flattering and present SubbaRow in a single dimension, a man fighting a racist organization, struggling to make ends meet and always a humble introvert. But in reality, he was a little more to the center, and quite an ordinary person, with a lot many virtues and a few faults or deficiencies. These become quite clear in the many interviews conducted by his first biographer Gupta, and thankfully uploaded in the Subbarow website, for others to peruse. These kinds of work pressures exist to this day on and some amount of discrimination is still evident but mostly as an undercurrent.

My interest in delving deeper started with this aspect - SubbaRow had informed Seshagiri that he had annulled their marriage and remarried in 1941, now what and who could that be? The interviews I perused are the ones Gupta had with YSR’s American colleagues, assistants, and supervisors.

Almost everyone highlights his astounding photographic memory, dominating personality, his punishing work ethic, his demands for total loyalty from his subordinates, and his boundless enthusiasm when he identified a cause to go after. Almost everyone noticed that he was very often in the American Cyanamides – Lederle lab premises at Pearl river at 6 o’clock in the morning and up until 1 or 2 o’clock in the morning. While he did ask often about the wellbeing of his assistants, he allowed just a handful to get close to him, and only one or two into his two-bedroomed apartment, lined with many books and spartan otherwise.

His eating habits were noticed by some of his colleagues, that he was an unhealthy eater, prone to putting on much weight. His longtime associate - Anne Irene Schivek Mowat, mentions - I believe it was Sparr’s Drug Store and he ate most of his meals there - his eating habits were very bad - his table manners were all right but he just didn't eat the proper food and he didn't eat enough or at regular hours.

Another important aspect we can note is that in the beginning, he got his way in his new lab, budgets and funds were approved, personnel hires were quickly approved, but as the company got bigger, issues cropped up and so also the many frustrations and the demand for all the administrative work. His spare time was spent in trivial pursuits - Mowat believed that he took up flying and bowling out of sheer boredom - not because he was sociable - his social life was of his own choosing. She continues - He was lonely, but I think this was the structure of the man, I think he was so wrapped up in his work he wanted his time for himself to spend the way he wanted.

There is one intriguing aspect in his life, especially the background SubbRow presented to some of his friends as well as the Baptist church he was associated with. Almost all accounts establish that SubbaRow sailed from Bombay to Boston, via London. Mrs Mowat, Torgersen and some others were led to believe by YSR that he spent a year in London and acquired an MD in tropical sciences there. In fact, he also went on to tell them about his difficult existence in London, having had to eat meat and so on. Was he trying to garner sympathy? Perhaps! In reality, he embarked from Bombay in Sept 1923 and arrived Boston In Oct 1923. After completing tropical medicine at Boston, he started his PhD efforts in 1924, but completed it only in 1930.

Interesting tidbits abound, that he was a bad driver, scaring his passengers, sitting back, looking through the steering wheel and racing away in his car. He often met with the famous Coomaraswamy in New York. We can also note that at times, he was opinionated, short-tempered and sometimes quite vindictive. He never drank, but used to smoke often and then stopped it entirely. He did like praise and did want honors. All in all, what we should learn from the above, is that SubbaRow was a simple human being, not always a paragon of virtues, but a great human being, nevertheless.

Most of his colleagues called him Sub and noticed how his voice went up in pitch as he got excited and his diction somewhat difficult to figure out, at that instant. The Mowat’s state that SubbaRow expected his team to be totally focused on work and did not really appreciate social commitments such as marriage, children, and the such. But as his prosperity increased, he treated himself to a new car, and involvement in many activities such as riding, bowling, flying, archery and so on

The most important chapter in his short life was very personal and involved a congenial, personable, and sociable lady named Doris McKenzie hailing from Florida, who arrived at Lederle in 1943, as Dr Hill’s research associate and later became a chemist under SubbaRow. While SubbaRow hardly talked about the relationship, his colleagues noticed and provided some pointers after his death. We can conclude from the discussions Gupta had with YSR’s colleagues that YSR was certainly enamored by Doris Mckenzie, socialized with her often (and getting closely associated with her Baptist church) and as one colleague mentioned - I think he loved her very deeply and he was frustrated. I don't think she could take him as her husband. Well, she couldn't anyway unless he got a divorce. Toward the end, he was trying to get his marriage annulled.

After his death, Doris was eased out of Lederle and she was quite miffed about it. A colleague added - At the time he died she was very much left out - I understand that she probably was the top paid person that he had - paid more than anyone else under him. She was really turning out results - after he died, she became discouraged and left. In fact, Doris (and a colleague) got to the apartment and opened the door to see him dead. Perhaps he died heartbroken, perhaps it was the telling pressure at work. Doris McKenzie continued her research with TB, cancer and chemotherapy, writing many papers as late as 1967 and working at the Departments of Medicine, Veterans Administration Hospital and the University of Miami School of Medicine, Florida.

Sheshagiri, his wife, said to Gupta later – “It is my misfortune that he did not come back. But our marriage served him to get the mission of his life fulfilled because it gave him the opportunity to get his medical degree and to go to USA for research."

Today, dermatologists treating psoriasis, oncologists working with cancer, physicians prescribing broad spectrum antibiotics, filaria patients and pregnant mothers, can all thank SubbRow for his untiring efforts to get them effective treatment, and sometimes, even a cure. Many of his contemporaries and subordinates earned their laurels from his support and hard work, but SubbaRow never demurred, receiving neither awards nor titles in that monochromatic period.

As Doron K. Antrim observed, "You've probably never heard of Dr. Yellapragada Subbarao. Yet because he lived, you may be alive and are well today. Because he lived, you may live longer.

References

In Quest of Panacea: Successes and Failures of Yellapragada SubbaRow - Sikharam Prasanna Kumara Gupta, ‎Edgar L. Milford

Yellapragada SubbaRow, a Life in Quest of Panacea– Raji  Narasimhan

Yellapragada SubbaRao Archives OnLine

The Emperor of All Maladies: A Biography of Cancer - Mukherjee, Siddhartha (2010).

With many thanks and due acknowledgment to SPK Gupta whose sources and interviews have been referred to, while preparing this article.