Man of Miracle Drugs-Dr. Yellapragada SubbaRow (1895-1948)

Dr. Yellapragada SubbaRow (1895-1948)He Transformed Science; Changed LivesMost of the famous scientists around the worldare known only for one major discovery thathas had a lasting impact on our lives : WilhelmRoentgen for x-rays, Marie Curie for radium, C VRaman for the scattering of light by liquids, P M SBlackett for cosmic rays, Ronald Ross for the lifecycle of the malarial parasite, Alexander Flemingfor penicillin – all awarded the Nobel Prize fortheir one major discovery.There have been a few scientists known for twodiscoveries : Albert Einstein for the photoelectriceffect and the theory of relativity, John Bardeenfor transistors and super-conductivity, HargobindKhurana for the genetic code and synthesis ofgene.Occasionally a scientist makes a large number ofdiscoveries albeit in only one field like RobertWoodward in organic chemistry.Then there are persons who have made importantcontributions but have not received the Nobel Prizeor equivalent honours like Jonas Salk who madethe first polio vaccine, Michael Heidelberger thefather of modern immunology, G NRamachandran who discovered the structure ofcollagen, the most abundant protein in our bodyand also laid the foundations for CT scan andNMR technologies.Rarely, extremely rarely, a person comes on theworld scene and transforms science and our livesby making a large number of major discoveriesin – and otherwise makes important contributionsto – more than one basic field and does not onlynot get a Nobel Prize but does not get to be knownby name to most people, including scientistsaround the world.I am referring to Yellapragada SubbaRow. Suchan individual is perhaps born once in a thousandyears or more. I do not believe there is any otherperson in the documented history of biology andmedicine over the last 5,000 years who made sucha large number of basic discoveries that areapplied so widely.SubbaRow was born in India in 1895 and he diedin USA in 1948 at the young age of 53.He went to the United States in 1923 aftergraduating from the Madras Medical College andworked at Harvard Medical School until 1940when he went to Lederle Laboratories to direct itsmedical research.The search he directed at Lederle Laboratories forantibiotics with wider range of cures than the thenavailable penicillin and streptomycin led to thediscovery of polymyxin widely used even today incattle-feed and aureomycin the first of tetracyclineantibiotics which all of us have had some time orthe other in our lives. Tetracyclines have savedmillions of lives over the last 50 years.Aureomycin was presented to medicine in 1948,the year SubbaRow died. It was the first broadspectrumantibiotic, that is, one effective againstboth gram-positive and gram-negative germs. Itwas thus more powerful than either Fleming’spenicillin or Waksman’s streptomycin.When SubbaRow’s centenary year began in 1994,tetracyclines – especially doxycycline – helpedconfine and then eradicate the plague epidemicthat broke out in Gujarat and Maharashtra. It wasa debt SubbaRow paid to his motherland almosthalf a century after death which claimed him soonafter the unveiling of Aureomycin before a medicalgathering at the New York Academy of Sciences.Doxycycline, the third generation tetracycline, hasrecently been cleared as a malaria preventive. Theinternational staff of the United Nations AssistanceMission in East Timor (UNMET) packed it in theirsurvival kits when ordered last year into the regionwrested from Indonesia.SubbaRow and his team of organic and biologicalchemists isolated folic acid from liver and amicrobial source and then synthesized it in 1945.By the clinical trials he organised, SubbaRow hadthe satisfaction of knowing that it cures tropicalsprue which took him to the death’s door while amedical student in Chennai and carried away twoof his brothers. It was subsequently found to curea variety of anaemias. The US government hassince January 1, 1988 required that all flour, pastaand other grain products be enriched with folicacid to stave off spinal-cord defects in newborns.In mid-1999 the New England Journal of Medicinereported that this has already reduced levels ofhomocysteine, an amino acid, among the USpopulation. Homocysteine is a risk factor incoronary heart diseases. Therefore that report hasstarted a debate whether folic acid can control asignificant cause of heart diseases.It is a pity SubbaRow is not given the credit forlaying the foundations for the isolation of VitaminB12 the antipernicious anaemia factor. Our dailyrequirement of B12 is just one microgram. That isall you require, but it is extremely important youget it. If you have those indescribable pains allover, chances are that you need it. SubbaRow spentyears trying to isolate it from liver and succeeded,but failed to recognise it. Others opened the doorhe found.In 1965 or 1966, I met Sir Alexander Haddow, avery distinguished and handsome scientist. He wasthen the director of the Chester Beatty CancerResearch Institute in London. We started talkingabout methotrexate which was being used widelynot for curing but alleviating the suffering fromBurkitt’s lymphoma, one kind of cancer, and hesaid, “Do you know that methotrexate wasdiscovered by an Indian?” You can imagine thesense of pride I felt.SubbaRow got aminopterin, which reverses theaction of folic acid, synthesized when reports of aclinical collaborator indicated that chemicalsresembling the vitamin arrest the growth of cancercells. He thus initiated the chemotherapeuticapproach to the treatment of cancer. Methotrexate,a derivative of aminopterin, has since then beenthe drug of choice in childhood leukaemia andmany adult cancers. Subsequently, methotrexatehas been used by doctors to control rheumatoidarthritis and psoriasis. More recently, it has beenemployed for medical abortion and in ectopicpregnancy and Crohn’s colitis. Now comes areport in Chest that low-dose methotrexate sparessteroid usage in asthma patients. There seems tobe no end to such new SubbaRow miracles!As Director of Research at Lederle, SubbaRowestablished a project for protecting Americansoldiers fighting in the Pacific from malaria andfilariasis. He found in Hetrazan the cure forfilariasis. It is today the most widely used drugagainst filariasis which leads to the deformitycausingelephantiasis. For years there washesitation in employing diethylcarbamazine (DEC),the generic name for Hetrazan, in massJournal, Indian Academy of Clinical Medicine Vol. 2, No. 1 and 2 January-June 2001 9798 Journal, Indian Academy of Clinical Medicine Vol. 2, No. 1 and 2 January-June 2001campaigns against the scourge of elephantiasisbecause of certain unpleasant side effects likenausea. The World Health Organisation (WHO)has found that these side effects were due tounnecessarily high dosages previously prescribedand that it was enough to administer only a singledose of DEC, concurrently with invermectin, tokeep blood free of filarial worms for a whole year.And WHO has made DEC a key element of itsworldwide campaign for the elimination ofelephantiasis.Let me go backwards in time. When I raise myhand I am consuming energy. We derive energyfrom the food we take. A good part of what weeat is converted by the body into glucose. Amechanism in the body metabolises glucose andin the process generates energy the muscles usefor running, raising hands, and doing the work ofeveryday life. That alone wouldn’t be enough.There must be ways of storing the energy obtainedfrom food because we are not eating food all thetime. There was a hunt therefore in the 1920s forthe chemical substances in the body acting asenergy stores on which the body draws wheneverit needs energy. It was SubbaRow who codiscovered,while working with Cyrus Fiske atHarvard, the two chemicals – phosphocreatine andadenosine triphosphate (ATP) - that store energyin our body. In fact, all living organisms storephosphocreatine as their source of energy. Whenthe body needs energy, ATP is converted into ADP(adenosine diphosphate) and ATP is replenishedby phosphocreatine while the body rests.Not only did he show how important phosphorusis for our body, SubbaRow also devised the perfectway of estimating phosphorus in living organisms.There may not be any biologist of any kindanywhere in the world who has not some time orthe other used the Fiske-SubbaRow Method ofestimating phosphorus. In all fairness it shouldhave been called the SubbaRow-Fiske method butSubbaRow put the name of his supervisor first onthe paper describing it.Trained first as a mathematician and physicist andthen as a chemist with no formal training inbiology, I got introduced to experimental biologythrough estimating phosphorus. And I used theFiske-SubbaRow Method. That was in 1953.Hailing from Andhra as I did, I remember askinghow he spelt his name Row and not Rao. As Ilearnt later he would have been the last man everto cause a row! If you look at citations of scientificpapers - which is the way others use your scientificwork and quote it in their publications - SubbaRowturns out to be one of the most highly cited scientistsin the entire history of science.Thus far about his work. What about the manhimself? I have a wish list of ten persons from thebeginning of human history I would have liked tomeet personally. In it figures SubbaRow along withChanakya, Ashoka, Leonardo da Vinci. I regret Inever knew him. My first visit to USA was five yearsafter he died but I have met and talked aboutSubbaRow with people who knew him intimately.What came through in these talks, apart from hisscientific brilliance, was his tremendous modestyand self-effacement. This was very difficult tounderstand as he was driven by a desire to befamous. But he was at the same time generous ingiving credit for what he had done to someonewho stood to gain a great deal thereby. It is difficultto reconcile these two qualities but all of us havea little bit of such contradictions in us.Fiske would not have got the position he did atHarvard but for SubbaRow sharing with him thecredit for the method of estimating phosphorus inbiological fluids. My friend, S P K Gupta, in hisbiography of SubbaRow has documented manysuch acts of his to get a friend or a colleague geta promotion or a job or an advantage.SubbaRow’s cultural pluralism is another thing thatcomes through in his documented life and workand in personal dialogues with people who knewhim. He had this multiplicity of backgrounds whichintermeshed in his personality: He was extremelyIndian and identified himself as an Indian. He wasconversant with our ancient scriptures and his earlywork was in Ayurveda. But he also providedJournal, Indian Academy of Clinical Medicine Vol. 2, No. 1 and 2 January-June 2001 99financial support to the Church, especially tochurches which seemed to have an universalelement in their beliefs and to their educationprogrammes. It is strange that while he was anIndian in reality always, an Indian visiting him inUSA told his family in India that SubbaRow hadbecome totally Americanised. Appearances canbe deceptive!We must give credit to the United States for givinghim the kinds of facilities to work not previouslygiven to any Indian. But there is another side tothe story that must be told. Let me quote from thebiography, In Quest of Panacea, some bits thatshow how politics operate in the world:“SubbaRow’s admission to the U.S. and his staythere for a quarter of a century was possiblebecause he went there as ‘a physician’ andqualified himself as a ‘chemist’ – two of theprofessions that were exempt from the ban onimmigration of Indians in force from 1917.”The Supreme Court ruled that Hindus were notCaucasians and the President excluded fromAmerican citizenship even those Indians who hadbeen legal immigrants and had met the minimumresidence requirement.“Although he could get his ‘student’ visa, originallyvalid for two years, periodically extended becausehe belonged to the excepted category, ‘he wasalways mortally afraid ... that he might be pickedup for some minor infraction of the law and beshipped back to India... Then came the SecondWorld War and the Alien Registration Act of 1940.SubbaRow had always to carry from then on acard bearing his right thumb impression, signatureand registered number (3420564) testifying to hisstatus as an ‘alien’, one of the 3896 East indianson the Registry. And he had to report his addressevery three months to the Department of Justicein Washington.“In 1942, he had to get special clearance becausehis position as Director of Research at Lederle wasconsidered sensitive in view of his supervision ofthe processing of blood albumin for supply to theNavy and of the research on tetanus and gasgangrene toxoid that was of interest to the Armyand the Navy. The clearance was given after adeclaration by his company that it ‘never had anyreason to doubt his devotion and allegiance tothe United States’ and a thorough investigationwas made of his record both at Boston and atPearl River.”The New Republic fulminated in 1943 against thenotion that natives of India like SubbaRow andother world-renowned scientists then playingvaluable roles in USA in helping to win the Warwere unfit for American citizenship that was ‘freelygranted to the most backward and ignorantBalkan peasant’. That year a number of bills wereintroduced in the Senate and the House ofRepresentatives for lifting the citizenship bar onIndians. One of them reached the statute book inJuly 1946.SubbaRow wished to shed the stigma of being an‘alien’ amidst people with whom he had lived 25years and had thrown his lot, but it took a year forhim to get the ruling of the Immigration andNaturalization Service that he had been admittedlegally into the United States. He spread the goodnews among his associates but he did not in thenext twelve months he lived file his ‘Declarationof Intention’ the necessary first step to get theAmerican citizenship.SubbaRow felt within he was an Indian and hedied an Indian.When he died on August 8, 1948, obituariesappeared in Science, New York Times, New YorkHerald-Tribune and newspapers and journals inmany parts of the world. The Herald-Tribune calledhim ‘one of the most eminent medical minds ofthe Century’.Yellapragada SubbaRow was not born great; hismother had to sell the little jewellery she possessedto provide for his education. Nor was greatnessthrust upon him. He achieved greatness byimagination, self-confidence, love of fellowhumans, and an inner compulsion to alleviatehuman suffering. And he did what no other Indianhad ever done till then on foreign soil: he madesome of the most important and seminalcontributions that were destined to transform awhole range of basic and applied sciences andsave innumerable human lives. If there were aNobel Prize for those who died virtually unknownbut whose accomplishments lit the path of manywho came later, SubbaRow would surely be amongthe first to receive it.Even today in our country very few people knowof him. The efforts of the Centenary Committeesucceeded in getting the government issue astamp in his honour in 1995. But he has notbeen given the appropriate recognition by thenation till today. We have given the Bharat Ratnaposthumously to others. Why not toYellapragada SubbaRow?

Man of Miracle Drugs-Dr. Yellapragada SubbaRow (1895-1948)

Comments

Activity