Dr. Yellapragada Subbarow (1895-1948) He Transformed Science; Changed Lives
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HISTORY OF MEDICINE Dr. Yellapragada SubbaRow (1895-1948) He Transformed Science; Changed Lives Pushpa Mitra Bhargava Woodward in organic chemistry. Then there are persons who have made important contributions but have not received the Nobel Prize or equivalent honours like Jonas Salk who made the first polio vaccine, Michael Heidelberger the father of modern immunology, G N Ramachandran who discovered the structure of collagen, the most abundant protein in our body and also laid the foundations for CT scan and NMR technologies. 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. I am referring to Yellapragada SubbaRow. Such an individual is perhaps born once in a thousand years or more. I do not believe there is any other ost of the famous scientists around the world person in the documented history of biology and are known only for one major discovery that M medicine over the last 5,000 years who made such has had a lasting impact on our lives : Wilhelm a large number of basic discoveries that are Roentgen for x-rays, Marie Curie for radium, C V applied so widely. Raman for the scattering of light by liquids, P M S Blackett for cosmic rays, Ronald Ross for the life SubbaRow was born in India in 1895 and he died cycle of the malarial parasite, Alexander Fleming in USA in 1948 at the young age of 53. for penicillin – all awarded the Nobel Prize for He went to the United States in 1923 after their one major discovery. graduating from the Madras Medical College and There have been a few scientists known for two worked at Harvard Medical School until 1940 discoveries : Albert Einstein for the photoelectric when he went to Lederle Laboratories to direct its effect and the theory of relativity, John Bardeen medical research. for transistors and super-conductivity, Hargobind The search he directed at Lederle Laboratories for Khurana for the genetic code and synthesis of antibiotics with wider range of cures than the then gene. available penicillin and streptomycin led to the Occasionally a scientist makes a large number of discovery of polymyxin widely used even today in discoveries albeit in only one field like Robert cattle-feed and aureomycin the first of tetracycline antibiotics which all of us have had some time or laying the foundations for the isolation of Vitamin the other in our lives. Tetracyclines have saved B12 the antipernicious anaemia factor. Our daily millions of lives over the last 50 years. requirement of B12 is just one microgram. That is all you require, but it is extremely important you Aureomycin was presented to medicine in 1948, get it. If you have those indescribable pains all the year SubbaRow died. It was the first broad- over, chances are that you need it. SubbaRow spent spectrum antibiotic, that is, one effective against years trying to isolate it from liver and succeeded, both gram-positive and gram-negative germs. It but failed to recognise it. Others opened the door was thus more powerful than either Fleming’s he found. penicillin or Waksman’s streptomycin. When SubbaRow’s centenary year began in 1994, In 1965 or 1966, I met Sir Alexander Haddow, a tetracyclines – especially doxycycline – helped very distinguished and handsome scientist. He was confine and then eradicate the plague epidemic then the director of the Chester Beatty Cancer that broke out in Gujarat and Maharashtra. It was Research Institute in London. We started talking a debt SubbaRow paid to his motherland almost about methotrexate which was being used widely half a century after death which claimed him soon not for curing but alleviating the suffering from after the unveiling of Aureomycin before a medical Burkitt’s lymphoma, one kind of cancer, and he gathering at the New York Academy of Sciences. said, “Do you know that methotrexate was discovered by an Indian?” You can imagine the Doxycycline, the third generation tetracycline, has sense of pride I felt. recently been cleared as a malaria preventive. The international staff of the United Nations Assistance SubbaRow got aminopterin, which reverses the Mission in East Timor (UNMET) packed it in their action of folic acid, synthesized when reports of a survival kits when ordered last year into the region clinical collaborator indicated that chemicals wrested from Indonesia. resembling the vitamin arrest the growth of cancer cells. He thus initiated the chemotherapeutic SubbaRow and his team of organic and biological approach to the treatment of cancer. Methotrexate, chemists isolated folic acid from liver and a a derivative of aminopterin, has since then been microbial source and then synthesized it in 1945. the drug of choice in childhood leukaemia and By the clinical trials he organised, SubbaRow had many adult cancers. Subsequently, methotrexate the satisfaction of knowing that it cures tropical has been used by doctors to control rheumatoid sprue which took him to the death’s door while a arthritis and psoriasis. More recently, it has been medical student in Chennai and carried away two employed for medical abortion and in ectopic of his brothers. It was subsequently found to cure pregnancy and Crohn’s colitis. Now comes a a variety of anaemias. The US government has report in Chest that low-dose methotrexate spares since January 1, 1988 required that all flour, pasta steroid usage in asthma patients. There seems to and other grain products be enriched with folic be no end to such new SubbaRow miracles! acid to stave off spinal-cord defects in newborns. As Director of Research at Lederle, SubbaRow In mid-1999 the New England Journal of Medicine established a project for protecting American reported that this has already reduced levels of soldiers fighting in the Pacific from malaria and homocysteine, an amino acid, among the US filariasis. He found in Hetrazan the cure for population. Homocysteine is a risk factor in filariasis. It is today the most widely used drug coronary heart diseases. Therefore that report has against filariasis which leads to the deformity- started a debate whether folic acid can control a causing elephantiasis. For years there was significant cause of heart diseases. hesitation in employing diethylcarbamazine (DEC), It is a pity SubbaRow is not given the credit for the generic name for Hetrazan, in mass Journal, Indian Academy of Clinical Medicine Vol. 2, No. 1 and 2 January-June 2001 97 campaigns against the scourge of elephantiasis then as a chemist with no formal training in because of certain unpleasant side effects like biology, I got introduced to experimental biology nausea. The World Health Organisation (WHO) through estimating phosphorus. And I used the has found that these side effects were due to Fiske-SubbaRow Method. That was in 1953. unnecessarily high dosages previously prescribed Hailing from Andhra as I did, I remember asking and that it was enough to administer only a single how he spelt his name Row and not Rao. As I dose of DEC, concurrently with invermectin, to learnt later he would have been the last man ever keep blood free of filarial worms for a whole year. to cause a row! If you look at citations of scientific And WHO has made DEC a key element of its papers - which is the way others use your scientific worldwide campaign for the elimination of work and quote it in their publications - SubbaRow elephantiasis. turns out to be one of the most highly cited scientists in the entire history of science. Let me go backwards in time. When I raise my hand I am consuming energy. We derive energy Thus far about his work. What about the man from the food we take. A good part of what we himself? I have a wish list of ten persons from the eat is converted by the body into glucose. A beginning of human history I would have liked to mechanism in the body metabolises glucose and meet personally. In it figures SubbaRow along with in the process generates energy the muscles use Chanakya, Ashoka, Leonardo da Vinci. I regret I for running, raising hands, and doing the work of never knew him. My first visit to USA was five years everyday life. That alone wouldn’t be enough. after he died but I have met and talked about There must be ways of storing the energy obtained SubbaRow with people who knew him intimately. from food because we are not eating food all the What came through in these talks, apart from his time. There was a hunt therefore in the 1920s for scientific brilliance, was his tremendous modesty the chemical substances in the body acting as and self-effacement. This was very difficult to energy stores on which the body draws whenever understand as he was driven by a desire to be it needs energy. It was SubbaRow who co- famous. But he was at the same time generous in discovered, while working with Cyrus Fiske at giving credit for what he had done to someone Harvard, the two chemicals – phosphocreatine and who stood to gain a great deal thereby. It is difficult adenosine triphosphate (ATP) - that store energy to reconcile these two qualities but all of us have in our body. In fact, all living organisms store a little bit of such contradictions in us. phosphocreatine as their source of energy. When the body needs energy, ATP is converted into ADP Fiske would not have got the position he did at (adenosine diphosphate) and ATP is replenished Harvard but for SubbaRow sharing with him the by phosphocreatine while the body rests.