This is the story of a person who transformed science and our lives by making a large number of major discoveries in several fields and who not only got a Nobel Prize but also did not bother about getting known even by name to most of the people, including scientists around the world. I am referring to Yellapragada SubbaRow. I do not believe there has been any other person in the documented history of Biology and Medicine over the last 5,000 years who made such a large number of basic discoveries that have been applied so widely.
SubbaRow was born in Bharat in 1895 and he died in USA in 1948 at the young age of 53. He went to the United States in 1923 after graduating from the Madras Medical College and worked at Harvard Medical School until 1940 when he went to Lederle Laboratories to direct its medical research. This led to the discovery of polymyxin widely used even today in cattle-feed, and aureomycin the first of tetracycline antibiotics which all of us have used some time or the other. Tetracyclines have saved millions of lives over the last 60 years. Aureomycin was the first broad spectrum antibiotic, that is, one effective against both gram-positive and gram-negative germs. It was thus more powerful than either Fleming’s penicillin or Waksman’s streptomycin.
When SubbaRow’s centenary year began in 1994, tetracyclines – especially doxycycline – helped confine and then eradicate the plague epidemic that broke out in Gujarat and Maharashtra. It was a debt SubbaRow paid to his Motherland almost half a century after death which claimed him soon after the unveiling of aureomycin before a medical gathering at the New York Academy of Sciences in 1946.
SubbaRow and his team of Organic and Biological chemists isolated folic acid from liver and a microbial source and then synthesised it in 1945. By the clinical trials he organised, Subbarow had the satisfaction of knowing that it cures tropical sprue which took him to the death’s door while he was a medical student in Chennai, and carried away two of his brothers. Folic acid was subsequently found to cure a variety of anaemias. The US government has since January 1, 1988, required that all flour, pasta and other grain products be enriched with folic acid to stave off spinal-cord defects in newborns. In mid-1999, New England Journal of Medicine reported that this enrichment has already reduced levels of homocysteine, an amino acid, among the US population. Homocysteine is a risk factor in coronary heart diseases.
It is a pity that SubbaRow has not been given the credit for laying the foundations for the isolation of Vitamin B12, the antipernicious anaemia factor. Our daily requirement of B12 is just one microgram, but it is extremely important that you get it. If you have those indescribable pains all over, chances are that you need Vitamin B12. SubbaRow spent years trying to isolate it from liver and succeeded, but failed to recognise it. Others opened the door he had discovered.
In 1965, I met Sir Alexander Haddow, director of the Chester Beatty Cancer Research Institute in London. We started talking about methotrexate – a derivative of aminopterin – which was being used widely for alleviating the suffering from Burkitt’s lymphoma, a kind of cancer, and he said, “Do you know that methotrexate was discovered by an Indian?” You can imagine the sense of pride I felt, for I knew it was SubbaRow.
SubbaRow got aminopterin, which reverses the action of folic acid,
synthesised when work of a clinical collaborator indicated that chemicals resembling aminopterin arrest the growth of cancer cells. He thus
initiated the chemotherapeutic approach to the treatment of cancer. Methotrexate, has since then been the drug of choice in childhood leukaemia and many adult cancers. Subsequently, methotrexate has been used by doctors to control rheumatoid arthritis and psoriasis. More recently, it has been employed for medical abortion and in ectopic pregnancy and Crohn’s colitis. Now comes a report in Chest that
low-dose methotrexate spares steroid usage in asthma patients. There
seems to be no end to such new SubbaRow miracles!
As Director of Research at Lederle, he established a project for protecting American soldiers fighting in the Pacific from malaria and filariasis. He found in Hetrazan the cure for filariasis. It is the most widely used drug today against filariasis which leads to the deformity-causing elephantiasis.
There was a hunt in the 1920s for chemical substances in the body acting as energy stores on which the body draws whenever it needs energy. It was SubbaRow who codiscovered, while working with Cyrus Fiske at Harvard, the two chemicals – phosphocreatine and adenosine triphosphate (ATP) – that store energy in our body. In fact, all living organisms use ATP as their store of energy. When the body needs energy, ATP is converted into ADP (adenosine diphosphate), and ATP is replenished by phosphocreatine while the body rests.
Not only did SubbaRow show how important phosphorus is for our body, he also devised the perfect way of estimating phosphorus in living organisms. There may not be any biologist of any kind anywhere in the world who has not some time or the other used the Fiske-SubbaRow method of estimating phosphorus. In all fairness it should have been called the SubbaRow-Fiske method but SubbaRow put the name of his supervisor first on the paper describing it. Subbarow is one of the most highly cited scientists in the entire history of science. What came through in these talks, apart from his scientific brilliance, was his tremendous modesty and self-effacement.
Dr SubbaRow had this multiplicity of backgrounds which intermeshed in his personality: He was extremely Bharateeya and identified himself as a Bharateeya. He was conversant with our ancient scriptures and his early work was in Ayurveda.
When he died on August 8, 1948, obituaries appeared in Science, New York Times, New York Herald-Tribune and newspapers and journals in many parts of the world. The Herald-Tribune called him ‘One of the most eminent medical minds of the Century’.
Yellapragada SubbaRow was not born great; his mother had to sell the little jewellery she possessed to provide for his education. Nor was greatness thrust upon him. He achieved greatness by imagination, self-confidence, love of fellow humans, and an inner compulsion to alleviate human sufferings. If there were a Nobel Prize for those who died virtually unknown but whose accomplishments lit the path of many who came later, SubbaRow would surely be among the first to receive it.
Our government issued a stamp in his honour in 1995, but he has not been given an appropriate recognition by the nation till today. We have given the Bharat Ratna posthumously to others. Why not to Yellapragada SubbaRow?
Pushpa Mittra Bhargava (The writer is the Founder-Director of Centre for Cellular and Molecular Biology in Hyderabad, and the former Vice-Chairman of National Knowledge Commission)
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